Creative Animodel totally understands that it is a challenging and long-time process to develop novel therapies especially anticancer regimens. As an experienced bioscience CRO, we would like to help you accelerate the process through our preclinical services including PD, PK, toxicology services and the establishment of tumor-bearing animal models, the supply of tumor cell lines and tissues, and the support of tumor related biotechniques.
Our highly experienced preclinical team has performed a huge number of PD, PK, and toxicology experiments to evaluate novel compounds. According to our detailed protocol, specific aspects of drug property and its mechanism of action are fully understood. During researches, the study results will be sent to clients in a timely and cost-effective manner. If necessary, clients can also work with our PD, PK or toxicology team to design the most appropriate protocol and monitor the whole experimental process.
In the past years, Creative Animodel has collected more than 80 cases of human tumors. At present, 30 cases are growing as subcutaneous xenografts in nude mice, and others were retained as nitrogen frozen samples. Tumors types comprise: stomach, lung, liver, pancreas, kidney, bladder, skin, breast, brain, colon, prostate, sarcomas (bone), uterus, ovary and hematological models. Also, we have a full range of human tumor cell lines that have been validated in our in vivo efficacy studies or reported in literature. According to the requirements from clients and our experience, Creative Animodel can offer subcutaneous, orthotopic, metastatic, transgenic and chemoinduced models using these tumor samples and cell lines.
Additionally, Creative Animodel provides powerful tumor-related biotechniques support for clients. Our services focus on in vitro and in vivo preclinical studies as well as toxicological, pathological, and toxicokinetics researches.
Creative Animodel has constructed systematic data and experience in pharmacology or oncology services. If you are interested in our laboratory, please contact us. Our research scientists will work closely with you to develop detailed study protocols to meet your goals.
Creative Animodel is a privately held Contract Research Organization (CRO) dedicated in providing PK/PD services to the pharmaceutical and biotech industries. Leveraging our extensive expertise and state-of-the-art facilities, Creative Animodel can quickly perform bioanalytical analysis to validate the sensitive and accurate of PK/PD assays in a number of different matrices from different species. Our scientists have extended experience working with plasma, urine, bile, tissue and cerebral spinal fluid (CSF), and will optimize the extraction conditions to provide a reproducible and robust method to help our clients’ drug development.
PK describes the quantitative relationship of concentration–time profiles in different body fluids (plasma, serum, blood, urine, saliva, and CSF, etc.), whereas PD quantifies the characterization of the intensity of effects resulting from certain drug concentrations at the hypothetical effect site. PK/PD analysis, which is critical to drug development, bridges these two once disassociated branches of pharmacology. Understanding the PK/PD behaviors of a drug helps designing the dose, route, and schedule of administration to maximize effectiveness while reducing adverse effects.
PK/PD Analysis at Creative Animodel
Creative Animodel performs PK/PD analysis in multiple species (rodents and non-rodents) with all routes including intravenous, subcutaneous, intraperitoneal, ocular and oral administration. Your compounds can also be administered to disease models, if required. Samples of blood, urine or other matrices, as well as tissues, are collected both pre- and post-dose to meet clients’ needs. Our bioanalytical laboratory contains GLP-compliant systems and qualified instrumentations, including immunoassay technical platforms as well as HPLC or multiple LC-MS/MS systems to provide sensitive, high-throughput evaluation of drug concentration in a variety of matrices. Our PK/PD Analysis includes:
• PK/PD program and protocol development and support
• Compartmental & noncompartmental analysis using WinNonlin®
• PK/PD modeling and simulation
• Bioavailability/bioequivalence studies
• Systemic PK and topical PK (brain, eye, carotid and jugular, etc)
• Drug distribution in tissue/organ and body fluid and determination of blood and brain ratio for brain penetration
• Metabolic kinetics with active metabolites
• Toxicokinetics data analysis
• Drug safety evaluation
• PK/PD reports
Creative Animodel has expertise in designing, performing, and interpreting the PK/PD studies. Our experienced teams have a deep understanding of PK/PD analysis and can provides our clients high quality and rapid turnaround services. Creative Animodel is your best partner to encourage your drug development.
Creative Animodel is a pioneer in bioequivalence studies and has considerable experience in the conduct of bioequivalence studies. Our clinical specialists are GCP-trained and have participated in numerous international clinical trials. We have fully GLP-compliant bioanalytical facilities with state-of-the-art laboratories managed by highly skilled and experienced scientific professionals. We guarantee our clients with high-quality and high-efficiency reports that comply with all statutory and applicable Global Regulatory Requirements.
Bioequivalence (BE) means that two or more products release their active ingredient into the bloodstream in the same rate and extent. It is determined based on the relative bioavailability of the innovator medicine versus the generic medicine. Bioequivalence studies are initiated to investigate differences between drugs, and they play a key role in the drug development period for both new drug products and their generic equivalents. In addition to requirements for new products, bioequivalence studies are also required by regulations to ensure therapeutic equivalence between a pharmaceutically equivalent test product and a reference product when a manufacturer changes the formulation of an existing product. With over 90% prescriptions in the US being fulfilled by generic drugs, the bioequivalence studies are crucial to the pharmaceutical industry. In order to bring a generic drug to the market, you need to be on speed with many key aspects. Our bioequivalence studies give you an assurance that your studies will benefit from superior resources, world class expertise and, more importantly, provide you confidence that you will be well equipped for the market application.
Bioequivalence Studies at Creative Animodel
Creative Animodel provides a full range of services for bioequivalence studies conducted by our experienced scientists. We have a strong SOP driven culture and ensure compliance with all statutory and applicable Global Regulatory Requirements. With our active volunteer database of 10,000 volunteers (healthy volunteers, special populations and female volunteers), Creative Animodel provides bioequivalence studies on healthy as well as patient population with various dosage forms to meet your requirements. Bioequivalence studies service package includes but is not limited to:
• Medical and scientific consultation throughout the study
• Protocol design and development
• Selection and evaluation of clinical sites
• Fasting and Fed condition studies
• Single and multiple doses
• Cross over and parallel studies
• BE study monitoring
• Data management and statistical analysis
• Study report for submission
Creative Animodel provides high-quality report with lower cost and shorter cycle time to meet your demands for developing pharmaceutical products. All analytical methods are developed and validated in line with current international regulatory requirements with assurance of precision recovery and stability checks. Creative Animodel is the best partner for your drug development.
Creative Animodel is a leading company specialized in new drug discovery and development. We can provide a comprehensive process for in vivo and in vitro drug metabolism and pharmacokinetic studies, including the integrated process of mass balance studies. Our team of experts with extensive experience can help you understand what you are trying to investigate and give you the most appropriate solutions. Our company strives to stay ahead of the changing research landscape. For drugs that are difficult to analyze with traditional mass balance procedures, our scientists also can provide the appropriate method such as accelerator mass spectrometry (AMS) to support your research.
What Can We Learn from a Mass Balance Study?
Mass balance study is a method to determine the absorption, metabolism, and excretion (AME) characteristics of a drug, which refers to balancing the amount of drug administered to the amount of drug-related material collected excreta (normally feces and urine, but expired air and sweat also involved). The primary objectives of mass balance study:
• To determine the absorption of drug after administration.
• To identify excretory pathways in early stages of drug development.
• To characterize the PKs of the intact parent drug and its metabolites.
• To determine clearance mechanisms, including metabolic and excretory fates and understand potential contributors of inter subject variability associated with drug–drug interactions (DDIs).
• To determine the organs/tissues distribution in preclinical species.
How Do We Perform a Mass Balance Study?
• A radioactive label (usually 14C) is incorporated into a drug before the drug administering.
• During the circulation (before the administered radioactivity is recovered in the excreta), blood, plasma, urine, and feces require accurate collected from the study subjects.
• The excreta and blood samples gathered in such studies are identified and quantified profiling of metabolites and parent drug by sensitive radiometric detection methods (liquid scintillation or accelerated mass spectroscopy).
Thus, the amount of “radioactivity” in the original dose can be compared to the amount of radioactivity in the excreta to calculate the mass balance. Since radioactivity measurements are independent of drugs’ chemical structure, total radioactivity measurements can be thought of as “parent + all metabolites”. Furthermore, the presence of the “label” has no impact on the identification of metabolites by LC/MS-MS methods combined with radiometric detection.
• Over 90% recovery ratio
• Ultrasensitive detection radiocarbon analysis
• Air pathway provided
• Richer Data Types (including PK parameters, concentration-time curves, cumulative recovery curves etc.)
Creative Animodel has innovative study designs, optimal facilities and strong regulatory intelligence, all of which will help our clients get high-quality results with lower cost and less time. A properly designed mass balance study will allow you to target address the main objectives with lower investment. Please contact us for further support in the development of your drug.
Creative Animodel offers a set of new drug in vivo tests and analysis that ranges from PK/PD analysis to drug safety evaluation to our global clients. In the aspect of drug safety evaluation, different detections are available to meet your special needs.
The Main Content of Drug Safety Evaluation
In the last 50 years, drug safety monitoring has developed rapidly in terms of increasing interest, broadening capacity, innovation of methods and availability of data. Safety is monitored through basic laboratory and clinical observations (e.g., heart rate, blood pressure, respiration, electrocar diogram), and being performed at frequent intervals throughout the expected duration of drug action. Clinical chemistry, hematology, and other appropriate laboratory observations are made at similar intervals. Special attention is paid to laboratory tests of organ function, especially critical target organs such as liver or kidney as well as the hematopoietic and reticuloendothelial systems, this is because toxicity is often due to loss of pharmacological selectivity by doses and concentrations increase. What’s more, special tests to monitor the activity of particular organs of interest (e.g., pulmonary function tests) may also be used to detect whether some drugs have side effect to special organs.
Drug safety evaluation, as an essential part of new drug discovery and development, we provide different assays to investigate the drug safety：
• Maximum Tolerated Dose (MTD) Study
The maximum tolerated dose (MTD) refers to the highest dose of a pharmacological treatment that causes dose-limiting adverse events in some predefined fraction of the subjects, abbreviated LD0. The purpose is to get information about the new drug’s safety. This type of analysis is also used in establishing chemical residue tolerances in foods. Maximum tolerated dose studies are also done in clinical trials. We provide different types of animal models to satisfy your research requirements.
• Dose Ranging Study
Dose ranging study gets knowledge of the relationships among dose, drug concentration in blood, and clinical response (effectiveness and undesirable effects), which is important for the safe and effective use of drugs. This study will give a comprehensive result of the new drug, including the appropriate starting dose, the adjust dosage and a maximum dose.
• Acute Toxicity Test
Acute toxicity describes the adverse effects of a substance that result either from a single exposure or from multiple exposures in a short period (usually less than 24 hours), which can provide preliminary information on the toxic nature of a new drug.
• Excellent quality management and quality assurance capacity
• Customize service for special requirements and shorter delivery time
• Both GLP standard study and Non-GLP standard assay
Creative Animodel strives to make the process of drug development easier by providing the research services, and the necessary guidance for the entire procedure. And we also have a worldwide reputation in the laboratory, what’s more, our products and services also get high reputation from our cooperated customers. Wish to cooperate with you in the near future.
Creative Animodel is a pioneer in toxicology services and dedicated to pharmaceutical/biopharmaceutical, biotech, academic research, medical device and related industries. We offer a comprehensive service for preclinical drug safety evaluation. Our services encompass toxicology, pharmacology, oncology, and metabolism testing. We deliver GLP and Non-GLP biological services to our clients in support of their drug development programs.
The maximum tolerated dose (MTD), an important part of preclinical toxicity test, describes the highest dose of a treatment or medicine that will produce the desired effect without causing unacceptable side effects or overt toxicity in a specific period of time. The MTD can be determined by acute toxicity studies, short duration dose escalation studies and dose ranging studies. These studies are designed with a minimum number of animals and include toxicological endpoints such as clinical observations and clinical pathology. Maximum tolerated dose is an essential aspect of a drug's profile. This information obtained from MTD can help guide the parameters for clinical trials to maximize safety and minimize risk. All modern healthcare systems dictate a maximum safe dose for each drug, and generally have numerous safeguards to prevent the prescription and dispensing of quantities exceeding the highest dosage which has been demonstrated to be safe for members of the general patient population.
Maximum Tolerated Dose Service:
With a decade of experience in drug safety evaluation, Creative Animodel performs pre-clinical toxicology studies in vivo to determine appropriate dosage, frequency and route of administration. Our scientists have an extensive experience to help clients determine maximum tolerable dose of their novel compounds for single and repetitive dosing. Our specifically tailored, individual study designs enable our clients to quickly meet their product development goals. Maximum tolerated dose service includes:
• Maximum tolerated dose (MTD): single or repetitive dosing.
• Multiple animal species including non-human primates, rats, mouse, rabbits, dogs, pigs, etc.
• Diverse routes including intravenous, subcutaneous, intraperitoneal and topical administration.
• 7-day or 28-day clinical observation: clinical signs (including body weight, food consumption and any other abnormal signs), morbidity and mortality.
• Ancillary services: clinical chemistry, urinalysis, hematology, blood gases, histopathology and macroscopic and microscopic necropsy.
Creative Animodel offers maximum tolerated dose (MTD) service for your drug safety evaluation. Our scientists, including toxicologists, pathologists, veterinary surgeons and regulatory specialists, have designed and performed numerous drug safety evaluation. With our skilled staffs, Creative Animodel can conduct standard as well as customized toxicology studies to meet clients’ need and regulatory requirements.
Creative Animodel offers acute toxicity tests for your drug safety evaluation. Our scientists, including toxicologists, pathologists, veterinary surgeons and regulatory specialists, have designed and performed numerous drug safety evaluation. With considerable experience in drug safety evaluation, Creative Animodel provides high-quality data and rapid turnaround period to support your drug discovery and development.
Acute toxicity, an important part of drug safety evaluation, describes the adverse effects of a pharmaceutical when it is administered in one or more doses during a short period time (less than 24 hours). To be described as acute toxicity, the adverse effects should occur within 14 days of the administration of the substance. Acute toxicity tests in animals are usually necessary for any pharmaceutical intended for human use. They provide information about possible dose levels for first applications to humans and indications as to the possible effects with over-dosing (accidental or intentional). The information obtained from these studies are crucial for choosing doses for repeat-dose studies, the evaluation of toxicological mechanism, the selection of starting doses for Phase 1 human studies, as well as providing information relevant to acute overdosing in humans.
Acute Toxicity Tests at Creative Animodel
Creative Animodel specializes in performing acute toxicity tests in both rodents and non-rodents with various administration routes available, such as intravenous, subcutaneous, intraperitoneal, ocular and oral. All abnormalities (including behavioral and clinical abnormalities or any other toxic effects as required by the client) caused by the investigational product during the experimental period are recorded. Morphological, biochemical, pathological, and histological changes in the dead animals are investigated. The toxicological evaluation from study design, daily observation to histology and pathology testing along with toxicokinetics studies are all compliant with GLP or NON-GLP standards. Creative Animodel provides a comprehensive range of services for acute toxicity tests to support your pre-clinical studies:
• Acute Dermal Toxicity
• Acute Oral Toxicity
• Acute Inhalation Toxicity
• Dermal Irritation/Corrosion
• Eye Irritation
• Skin Sensitization
• Vaginal Irritation Studies
• Local Lymph Node Assay
• Dermal and Eye Sensitization
• Acute Pre-neonatal and Neonatal Test.
Over decades of experience in drug safety evaluation, Creative Animodel has been an industry leader in the conduct of acute toxicity tests using various routes of administrations in different species. Our experienced scientists have a deep understanding of drug toxicity and can determine potential risk factors early in drug development process. Our customized services enable our clients to quickly meet their product development goals and timelines with a cost-conscious manner.
Creative Animodel is a global Contract Research Organization (CRO) and has been a trusted partner to leading pharmaceutical, biotechnology and medical device companies as well as academic and government organizations for decades. We offer a full spectrum of preclinical and clinical drug safety evaluation services utilizing state of the art facilities with our highly skilled staffs. With decades of experience in drug toxicology studies, Creative Animodel can deliver robust toxicity testing reports with streamlined turnaround to support customers’ drug development programs.
Dose ranging, known as dose range finding study, is a part of toxicity studies and usually carried out to find out the appropriate dose levels of a test article. The main goal of a dose-ranging study is to estimate the response vs. dose given, so as to analyze the efficacy and safety of a substance or treatment. The information obtained from dose ranging assessments is of great importance in assessing human risk.
Dose Ranging Service at Creative Animodel
Creative Animodel offers in vivo dose ranging service in both rodents and non-rodents with various routes, such as intravenous, subcutaneous, intraperitoneal, ocular or oral administration. Our experienced toxicologists can design and perform dose range finding study that includes dose escalation/maximum tolerated dose study to provide sufficient information to proceed to longer term studies. By measuring the impact at low, intermediate, and high doses as well as placebo groups, our team can demonstrate the no observed adverse effect level (NOAEL), which determines the highest dosage level at which chronic exposure to the substance shows no adverse effects, and the no observed effect level (NOEL), which reveals the dose-response relationship. Additionally, we provide preliminary identification of the target organs of toxicity as well as to dose selection for more definitive studies that are intended to support the clinical trials.
Creative Animodel offers a comprehensive range of services along the entire value chain of pre-clinical drug safety evaluation. With a consultative, flexible, integrated and multi-disciplinary approach, we offer the advice, answers and services to promote your drug to the market.
Large Molecule PK/BA Services
Creative Animodel has a brilliant history of providing the large molecule Pharmacokinetics (PK) and bioanalysis (BA) service with adherence to GLP regulations to advance the pharmaceutical industries. Equipped with the state-of-the-art technical platforms, our studies are performed by an innovative expert team that ensures consistent, high-quality, and on-budget data, with a fast turnaround time.
Large molecule drugs, referred to as biologics, are protein-based drugs, which are manufactured in living cells or contain components of living organisms by biotechnology, while the traditional small-molecule drugs are often manufactured via chemical synthesis. As the most advanced therapies available, biologics have been widely applied to treatment of numerous diseases and conditions, especially those hard-to-treat ones, like cancer.
Why Do We Highlight Large Molecule PK/BA Services?
Large molecules are different from small molecules in many aspects, such as size, behavior, mode of action, suitability for certain drug forms and manufacturing process, etc. Compared to small molecule drugs, large molecule drugs require approximately five times of quality assurance tests to ensure purity, potency, and quality. Because with a more complex structure, large molecules are often hundreds of times the size of small molecules, which are highly sensitive to temperature and pH, and susceptible to minor changes of conditions, likely leading to an increased risk of unexpected immune responses. All these factors drive the special concerns for large molecule PK/BA services.
Large Molecule PK/BA Services at Creative Animodel
The large molecule PK/BA services at Creative Animodel aim at studying the in vivo pharmacokinetics (PK), toxicokinetics (TK), immunogenicity (ADA), and immunoassays of large molecule drugs like monoclonal antibodies, antibody drug conjugates (ADCs), bispecific antibodies.
Creative Animodel is a leading contract research organization providing cell line-derived xenograft models to conduct pre-clnical drug screening, treatment evaluation and fundamental studies. Our experienced scientists and professional technical platforms enable us to deliver reliable results in a cost-efficient manner.
What Are Cell Line-Derived Xenograft Models?
Cell line-derived xenograft (CDX) model is a traditional and common tumor model type for disease studies and anti-tumor drugs development. Cell line-derived xenograft models are created by inoculating tumor cell lines into immune deficient mice or rats. And these cell lines can be engrafted subcutaneously, intravenously or orthotopically.
Figure 1. Xenografts derived from cell lines (Perez M et al., 2016)
For decades, Cell line-derived xenografts have been the most commonly used models to study cancers in mice. Because of user-friendly techniques and good repeatability, CDX models are still applied at the early stage of in vivo study. Moreover, CDX models provide important information to allow an agent to move forward and clients to advance their preclinical research in a cost-effective manner.
Cell Line-Derived Xenograft Models at Creative Animodel
Creative Animodel has established a comprehensive range of validated CDX models to satisfy clients in vivo research needs. What’s more, we also provide customized services aiming at personal requirements. Our all-around services involve CDX models construction, in vivo pharmacology projects execution as well as the final results presentation.
Creative Animodel is a contract research organization providing pharmacological services based on our disease models. With years of experience, our professional scientists have established various patient-derived xenograft models to help our clients to study diseases and facilitate drug development. We are confident to offer optimal experiment plans and execution.
What Are Patient-Derived Xenograft Models?
Patient-derived xenograft (PDX), also known as patient-derived tumor xenograft (PDTX), is created by transferring primary tumors from the patient into an immunodeficient mouse or rat. Tumors can be engrafted heterotopically or orthotopically. Heterotopic PDX models involve implanting tumors into the subcutaneous flank of a mouse, which allows for easier cell transfer and precise monitoring of tumor growth and location. While orthotopic models involve direct implantation to mouse organ of choice, which is more technically challenging and time consuming but is considered to be more accurately mimicing human tumors. As shown in Figure 1, fresh tumor tissues are obtained and then section them into pieces, followed by subcutaneous or orthotopic implantation into an immunodeficient mouse or rat. During the engraftment phase, tumors are allowed to establish and grow and then are harvested upon reaching a size of 1500 mm3. Similar protocols are employed for subsequent expansion cohort and treatment cohort.
Figure 1. Overview of the methodology to establish PDX models and their uses in cancer research. (Lai Y, 2017)
Why Choose Patient-Derived Xenograft Models?
PDXs have some biologically stable characteristic, such as global gene expression patterns, mutational status, metastatic potential, drug responsiveness and tumor architecture, which may provide improvements over standard cell-line xenograft models. What’s more, establishing tumors models from patient-derived tumor tissue is generally agreed to conserve original tumor characteristic in terms of clinical biomolecular signature, tumor architecture, and tumor vasculature. With these characteristics, PDX can provide predictive viewpoints about evaluating the efficacy of novel cancer therapies.
Highly immune deficient mice that can be successfully transplanted with a wide variety of tumors are used in our company. The mice have almost no rejection of human tissues and high efficiency in establishing PDX models. Moreover, subcutaneous, orthotopic, and disseminated models are available depending on clients’ needs.
• Cancer types.
We provide numerous PDX models covering most cancer types, including both solid tumor and blood cancer, such as brain cancer, bladder cancer, breast cancer, ovarian cancer, pancreatic cancer, lung cancer and acute myeloid leukemia.
We offer detailed annotation about our PDX models, including patient information, diagnosis, genomic profiling and so on.
With PDX models, we can conduct studies including preclinical drug screening, in vivo and ex vivo efficacy testing, preclinical combination therapeutics screening as well as identification and analysis of biomarkers.
We offer customized study designs to accommodate effectiveness of novel drugs or existing therapeutic compounds depending on clients’ needs.
Creative Animodel provides a wide variety of patient-derived xenografts models to further facilitate drug development process in a fast and cost-efficient manner. Our high-quality services and reliable results make it possible to meet various demands of our clients. If you have any questions, please feel free to contact us.
Obesity is defined as being more than 20% (in men) or 25% (in women) overweight. The World Health Organization (WHO) estimates that 10 % of the world’s adult population was obese. Obesity is increasing rapidly throughout the developed world and has increased from 13% to 31% in the US in the past 30 years. Meanwhile the global incidence of obesity is continuing to rise. Currently, scientists already made a huge effort to minimize the negative effects of obesity and decrease its overall prevalence throughout the world.
Obesity is a globally widespread disease. The primary causes of obesity are excessive calorie intake and lack of physical activity. Obesity is also a major risk factor for cardiovascular disease, diabetes, stroke, certain cancers, osteoarthritis, gastrointestinal, reproductive disorders and pulmonary diseases. The incidence of obesity continues to climb, making it imperative that animal models sharing characteristics of human obesity and its co-morbidities be developed in the quest for novel preventions and treatments.
Fig 1. A brief system for the obesity models. (Maruvada P. et al, 2017).
Creative Animodel provides various in vivo animal models and in vitro cell culture models to investigate the mechanism of obesity and novel therapeutics to treat human obesity (Figure 1). With Creative Animodel, you get more than a highly qualified CRO, you gain a partner, who understands and has the experience to design, validate and execute all preclinical program requirements.
Obesity Models Services at Creative Animodel
Creative Animodel offers a complete suite of animal models and services for the evaluation of novel therapeutics. We are dedicated to providing our customers with the most suitable animal models of obesity to advance the development of potential therapeutics in clinical studies. We will work closely with you on every step for obtaining meaningful and suggesting data from animal model studies for obesity. Although none of the models can completely capture the complexity of human metabolic syndrome, each model mimics certain aspects of the disease. Our featured animal models include, but are not limited to:
• Non-human primates: DIO (diet-induced obesity) rhesus macaques & DIO cynomolgus macaques
• High fat diet mouse/rat
• DIO mouse/rat
• Age-related obesity in mice
• Transgenic (monogenic and polygenic) mouse/rat
• Mini-pig model
Our studies of obesity are mainly divided into four types:
• Energy expenditure test of obesity
• Body composition analysis of obesity
• Dietary-induced obese animal
• Genetic obese animals
Mammals are often used for scientific research due to their close biological resemblance to humans. Human cell lines or diseases can be introduced into these species for experimentation, particularly rodents genetically engineered to remove part or all of their immune system so that foreign biological material is not rejected by the immune system.
High quality science and specialized knowledge are cornerstones of Creative Animodel's specialty services. All our disease models are fully validated to ensure the highest level of accuracy, reproducibility and consistency.
Central Nervous System Models (CNS Models)
Alzheimer's Disease Models
Amyotrophic Lateral Sclerosis (ALS) Models
Huntington's Disease Models
Multiple Sclerosis (MS) Models
Parkinson's Disease Models
Spinal Cord Injury Models
Stroke & Brain Ischemia Models
Traumatic Brain Injury Models
Creative Animodel is a professional biopharmaceutical company dedicated to providing preclinical in vivo pharmacology services for your drug candidate. With years of experience and advanced technology platform, we have successfully established a variety of nonalcoholic fatty liver disease (NAFLD) models to help our customers promote their drug development. Our scientists have deep expertise to guarantee the high-quality services with competitive price and fast turnaround time.
What Is NAFLD?
NAFLD is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse. There are various factors that can contribute to NAFLD, including diet, overweight, insulin resistance, a sedentary lifestyle, as well as genetic factors. NAFLD can be classified into two major types: simple steatosis and nonalcoholic steatohepatitis (NASH). NASH is considered as the most severe type of NAFLD. In NASH, not only steatosis but also intralobular inflammation and hepatocellular ballooning are present, often accompanied by progressive fibrosis. Long-standing NASH may progress to liver cirrhosis, and hepatocellular carcinoma (HCC) may be an outcome.
Figure 1. The differences between healthy Liver and fatty liver
The morbidity of NAFLD has been increasing worldwide over recent decades in line with the increased prevalence of obesity, type 2 diabetes, and hyperlipemia. NAFLD/NASH is currently regarded as the most common chronic liver disease worldwide. It is estimated that about 20% of all adults have NAFLD and 2%-3% of adults have NASH. However, there is still no regulatory agency-approved pharmacotherapy for NAFLD/NASH, with a lack of detailed knowledge of the underlying mechanisms. Further research on pathogenic pathways and potential drug treatments is crucial, given the rapid growth in NAFLD prevalence.
Our NAFLD/NASH models
Creative Animodel offers professional preclinical pharmaceutical services with extensive expertise based on the following super-class NAFLD/NASH models:
• High‐fat diet (HFD) model
The association between NAFLD/NASH and obesity leads to the development of an HFD that matches modern Western diets. Feeding animal with a diet composed of 71% fat, 11% carbohydrates and 18% protein for 3 weeks, we have successfully established HFD induced NAFLD/NASH model. This model mimics clinically relevant features of NAFLD over a prolonged period of time.
• Methionine and choline deficient (MCD) model
The MCD is a widely employed diet in NAFLD/NASH animal studies. MCD diet is high in sucrose (40% sucrose) and fat (10% fat), and is deficient in methionine and choline, which are essential for hepatic β oxidation and the production of very low density lipoprotein (VLDL). MCD diet induced model shows the features of NASH-related inflammation and fibrosis that have been implicated in human NASH progression.
Dyslipidemia and Atherosclerosis Models
Creative Animodel is a preclinical biopharmaceutical company that offers outstanding pharmacology consultancy and research services, and specializes in metabolic disorders such as diabetes, obesity, dyslipidemia, atherosclerosis and cardiovascular complications. Our staffs are led by senior scientists with rich international drug discovery experience, enabling the high-quality data with competitive price and fast turnaround time.
The Relationship Between Dyslipidemia and Atherosclerosis
Atherosclerosis is a multifactorial disease composed of a multitude of pathogenic developments, including macrophage foam cell formation and death, accumulation of extracellular lipid, chronic inflammation and the proliferation of intimal smooth muscle cell creating a fibro-fatty plaque. Those soft plaques could suddenly rupture with the subsequent transformation to thrombus that rapidly slow or stop blood flow, leading to a heart attack, stroke or a sudden cardiac death. A number of genetic and environmental factors contribute to its development.
Dyslipidemia, a major risk factor for atherosclerosis and consequent cardiovascular disease (CVD), is a disorder of lipoprotein metabolism, including lipoprotein overproduction or deficiency. Dyslipidemia, along with insulin resistance, obesity and type 2 diabetes, comprises an important component of the metabolic syndrome. Numerous epidemiological and clinical studies have identified that there is a strong association between certain types of dyslipidemia (such as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, phytosterolemia, etc.) and development of atherosclerotic lesions.
Atherogenic dyslipidemia has emerged as an important risk factor for myocardial infarction and cardiovascular disease, which constitutes a public health problem in terms of the cost for society and the quality of life for patients. Many clinical and experimental attempts have been made to understand the pathophysiology of this disease.
Dyslipidemia and Atherosclerosis Models at Creative Animodel
With state-of-the-art facilities, our experienced scientists have successfully established a range of dyslipidemia and atherosclerosis models to mimic the human condition, analyze pathogenesis, and evaluate the efficiency of your drug candidates.
• High-Cholesterol Diet (HCD) Model
HCD is widely used in dyslipidemia and atherosclerosis animal studies. HCD can increase the concentration of pro-atherogenic lipoproteins in the blood. We provide the well-characterized dyslipidemia and atherosclerosis model via feeding animal with HCD. This model has lots of similarities to human atherosclerosis in terms of the disease course and progression.
• Transgenic Models
Gene manipulation has been used to increase sensitivity to cholesterol in mice and rat. Creative Animodel uses transgenic technology to generate a number of genetically modified models, which show atherosclerotic changes in the aorta resembling human disease. We have various transgenic models including ApoE-KO model, LDLR-KO model and PCSK9 model to help you evaluate the efficiency and safety of your drug candidates.
Creative Animodel has a team of scientists skilled in animal model generation and preclinical in vivo drug trials. We work closely with our partners to identify, design and execute joint research activities more efficiently and more strategically so that milestones are met as quickly and efficiently as possible. If you have any questions, please feel free to contact us.
Mammals are often used for scientific research due to their close biological resemblance to humans. Human cell lines or diseases can be introduced into these species for experimentation, particularly rodents genetically engineered to remove part or all of their immune system so that foreign biological material is not rejected by the immune system.
High quality science and specialized knowledge are cornerstones of Creative Animodel's specialty services. All our disease models are fully validated to ensure the highest level of accuracy, reproducibility and consistency.
Human Tumor Xenograft in Nude Mice/Rats
Orthotopic Tumor Models
Intratibial Tumor Models
Murine Tumor Xenografts
Patient-Derived Tumor Grafts
Carrageenan Footpad Edema (CFE) Model
Collagen-Induced Arthritis (CIA) Model
Pristane-Induced Arthritis (PIA) Model
Adjuvant-Induced Arthritis (AIA)
Ovalbumin-Induced Arthritis (OIA)
Air Pouch Model
Delayed-Type Hypersensitivity (DTH) Mode
Central Nervous System Models (CNS Models)
Alzheimer's Disease Models
Amyotrophic Lateral Sclerosis (ALS) Models
Huntington's Disease Models
Multiple Sclerosis (MS) Models
Parkinson's Disease Models
Spinal Cord Injury Models
Stroke & Brain Ischemia Models
Traumatic Brain Injury Models
Metabolic Disease Models
Corneal wound healing
Chronic obstructive pulmonary disease (COPD) Model
Bleomycin-Induced Pulmonary Fibrosis Model
Models for other indications are also available for specific interests.
Creative Animodel is a leading biotech company, who has years of established experience in in vivo pharmacology researches. We provide various cough models that are reliable, robust and reproducible to assist the clients in profiling and evaluating the efficacy and side effects of novel therapies under development prior to testing in humans.
Cough Reflex and Disease
Cough, an important reflex defense mechanism, is a universal experience in health and an extremely common feature of many respiratory diseases, such as asthma. Cough affects nearly 10% of the general population, in which chronic cough (or persistent cough that lasts for more than 8 weeks) is responsible for around 20% of respiratory outpatient referrals.
Coughing arises when the cough receptor in the larynx and lung is stimulated, which evokes the irritation of sensory vagus nerves and afferent fibers to provide input to specific brain regions. The brain stem medullary central cough generator, under the control of the cerebral cortex, coordinates the efferent output to respiratory muscles and produces the cough effort. Abundant factors in both airways and the brain stem are involved in the enhancement of the cough reflex, among which the most potential factors are inflammatory mediators (TNF-α, histamine and LTD4), neuropeptides (CGRP and PGE2) and vanilloid receptors (TRPV1).
Figure 1. Representative scheme of the pathophysiology of cough reflex.
Establishment of cough model in animals that reflects the disease in humans is essential for investigating the pathogenesis and adaptation of cough reflex hypersensitivity, and enables pharmacological researches for developing therapy of cough.
Creative Animodel provides multiple animal models of cough to establish the efficacy and side-effect profiles of novel therapies prior to testing in humans. There are two types of cough models to satisfy the specific needs of pharmacological researchers:
• Cough models: induced by standard challenge agents in naïve animals.
• Exacerbated cough models: induced by challenge agents following exposure to substances such as
allergen and cigarette smoke.
Alternative inducers including citric acid and capsaicin are used in model establishment on rabbits, guinea pigs, or other species asked.
Model Characteristics and Pharmacology Evaluation
• Latency of cough onset
• Frequency of coughs min-1
• Total number of coughs
• Respiratory parameters
• Plasma for PK analysis
• Reliable, robust and reproducible cough models
• Comprehensive evaluation
• Cost efficiency with short duration
Creative Animodel is the best partner in pharmacological researches on drugs in the discovery and development process. We have a group of scientists with deep therapeutic expertise in respiratory diseases and provide a methodological guarantee for profiles of your drug candidates on cough intervention. We are looking forward to cooperating with you.
Pulmonary Fibrosis Models
Creative Animodel is one of the leading-edge experts among the frontier of pre-clinical model building service. We provide mouse and rat models of bleomycine-induced pulmonary fibrosis for clients all over the world. Based on the experienced scientists and unparalleled technique platforms, Creative Animodel guarantees the customers the most reliable and efficient services to achieve their goals.
Overview of Pulmonary Fibrosis
Pulmonary fibrosis is a chronic and irreversible respiratory disease where the scars are formed in the lung tissue. Along with the process of fibrosis, the tissue around and between the air sacs becomes thickened and stiff, leading to the reduction of oxygen supply in the blood, which further results in progressive shortness of breath. In addition, patients can also suffer from chronic dry cough, fatigue and weakness, discomfort in the chest, aching muscles and joints and unexplained weight loss.
Figure 1. Diagram of pulmonary fibrosis
Pulmonary fibrosis can result from multiple factors including long-term exposure to certain toxins, certain medical conditions, radiation therapy and some medications. However, in most cases of pulmonary fibrosis, the cause is never found, which is called idiopathic pulmonary fibrosis (IPF). Therapies including Pirfenidone and Nintedanib have been approved for IPF treatment, however, the incidence of IPF still keeps increasing. The goals of pulmonary fibrosis intervention for pharmacological researchers are to reduce the symptoms, attenuate or stop disease progression, prevent acute exacerbations, and prolong survival.
Bleomycin-induced Pulmonary Fibrosis Models
Bleomycin-induced pulmonary fibrosis, most prevalent in rodent models, is a useful pre-clinical model of human lung fibrosis. Bleomycin is a chemotherapeutic antibiotic, whose application in animal models bases on the fact that fibrosis is one of the major side effects of bleomycin on cancer treatment. Bleomycin leads to inflammation and fibrotic reactions within a short period of time, making it a practical tool for pathobiological studies and novel compounds evaluation in pre-clinical researches. Creative Animodel has developed bleomycin-induced pulmonary fibrosis on mice and rats. The test compound can be delivered by multiple routes including oral, inhalation, intravenous or subcutaneous administration.
Model Characteristics and Pharmacology Evaluation
• In-life parameters of clinical symptoms: respiratory measurement, body weight, daily activity levels, survival…
• Histopathology: fibrotic markers and Ashcroft score
• Collagen quantification: Sircol collagen assay and hydroxyproline assay
• Bronchoalveolar fluid (BALF) analysis: cytological analysis and cytokine ELISA
Creative Animodel offers professional models of pulmonary fibrosis for therapeutic as well as prophylactic studies. We are the best in scientific knowledge, expertise, data quality, timelines, flexibility and personal contacts. We are looking forward to cooperating with you.
Lung Inflammation Models
Creative Animodel is an ideal partner in in vivo pharmacology researches during the drug discovery and development process. With years of dedication, our scientific team has accumulated rich experience
Failure to remove these cells, therefore, can lead to robust numbers of infiltrating activated granulocytes in the injured site, which in turn progresses to chronic inflammation. Lung inflammation is a critical component of many chronic pulmonary diseases, including asthma, chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis.
The resolution of lung inflammation has been identified as an active and highly regulated cellular and biochemical process. The attenuation of pro-inflammatory mediators, activation of endogenous anti-inflammatory lipid mediators, phagocytic clearance of apoptotic cells, phenotype switching of inflammatory cells from pro- to anti-inflammatory status and lung mucociliary clearance of infective factors assist in the successful resolution of lung inflammation.
Lung Inflammation Models at Creative Animodel
An important goal in pharmaceutics is to achieve anti-inflammatory strategies by blocking or suppressing specific cytokines and chemokines that trigger and amplify lung inflammation. Creative Animodel establishes lung inflammation models induced by LPS or tobacco smoke.
Creative Animodel is a leading biotech company providing a holistic approach of in vivo pharmacology. We have developed comprehensive animal models to help you understand the efficacy of the new drug entities in a wide range of therapeutic areas. Our established experience can efficiently assist the clients in potential drug candidate screening as well as proof-of-concept studies for profiling of novel reagents targeting anti-inflammatory therapies for treatment of asthma.
The Pathology of Asthma
Asthma is a chronic inflammatory disorder of the airways, which is related to allergy and infections with respiratory viruses. Asthma causes recurring episodes of wheezing, chest tightness, breathlessness, and coughing. Particularly, cough caused by asthma can lead to widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment. The pathology of asthma is the airway hyperresponsiveness and remodeling result from the inhalational exposures with allergy and/or respiratory viruses’ infections. In the case of allergens, allergen-specific immune responses include Th2-induced IgE production, degranulation of mast cells, cascade reaction of airway epithelial cells and vascular cells, recruitment of eosinophils and neutrophils, and finally the damage of structural lung cells.
The knowledge of the molecular mechanism underlying asthma is essential for therapy development by targeting specific components of the pathological progress. Creative Animodel provides a serious extensively used asthma models to evaluate the therapeutic effect of innovative agents and candidates. Our models include but not limited to:
• OVA induced asthma in rats and mice
• OVA induced asthma in non-human primates
• House dust mite-induced asthma in rats and mice
• House dust mite-induced asthma in non-human primates
Model Characteristics and Pharmacology Evaluation
• Migration of inflammatory cells into the lung tissue: histopathology analysis of infiltration, cell count and
classification in broncho-alveolar lavage fluid (BALF)
• Serum level of IgE: total and OVA-specific IgE
• Release of inflammatory mediators: protein and mRNA levels of IL-4, IL-5 and IL-13 in BALF and lung tissue
• Lung function test: airway hyper-responsiveness and Penh method
• Multiple asthma models that meet your needs
• State-of-art technical platform
• Comprehensive analysis with integrated data delivery
• Cost efficiency in short period
Creative Animodel provides integrated in vivo pharmacology solutions to understand your drug candidates on asthma. Our in-house scientists with deep therapeutic expertise will help you to design, validate, conduct and analyze the animal efficacy studies, which will maximize the scientific value in the drug discovery and develop process. If you need any efficacy answers of your drug, please do not hesitate to contact us.
Acute Lung Injury Models
Creative Animodel has been a preclinical contract research organization (CRO) for decades. We offer a full range of pre-clinical drug evaluation services and are specialized in models of acute lung injury induced by LPS, acid aspiration, hyperoxia, cecal ligation and puncture and many more. Creative Animodel offers integrated pharmaceutical services for the global scientific community and provides an exceptional client-centered experience to advance the drug discovery process.
What Is Acute Lung Injury?
Acute lung injury (ALI) and its most severe manifestation, the acute respiratory distress syndrome (ARDS), are a life-threatening condition associated with an estimated incidence of 190,000 cases and 74,500 deaths per year in the United States alone. ALI is characterized by neutrophilic inflammation of the lung and decrease of lung compliance that can result in severe pulmonary edema leading to impaired pulmonary gas exchange. Clinical ALI is associated with specific risk factors that can be broadly divided into intra-pulmonary conditions, including pneumonia and pulmonary trauma; and extra-pulmonary risk factors, including extra-pulmonary sepsis, trauma, and pancreatitis.
In the past decade, the fundamental mechanisms that initiate and propagate the lung injury have not been defined completely, although considerable advances have been made in the understanding of the pathophysiologic mechanisms, diagnostics and therapeutics of ALI. However, there are still no approved treatments that will reverse the lung destruction during ALI. The clinical focus and overall goals are to provide ventilator support while minimizing the deleterious effects of mechanical ventilation on the lung in the form of ventilator-induced lung injury. Therefore, new therapies that decrease the magnitude of lung injury and hasten lung repair are needed.
ALD Models at Creative Animodel
Animal models are of considerable value for improving our understanding the mechanisms behind the ALI and developing treatment strategies. With years of efforts, Creative Animodel has established several ALD models in an attempt to reproduce the features of human ALI in animals.
Schizophrenia Disease Models
Schizophrenia is a chronic and severe mental disorder that affects approximately 1% of the population worldwide. It usually appears in early adulthood or late adolescence, and can often be a lifelong struggle, in terms of individual suffering as well as social impact.
Schizophrenia Disease Models and Tests at Creative Animodel
Animal models of schizophrenia at Creative Animodel serve for two main purposes. First, they may be heuristic, providing a framework in which to ask questions about etiology. Second, they may be predictive, i.e., used to test potential antipsychotic treatments, since animals and humans to a large extent share similar neuro-chemistries and neuro-circuitries of the brain. Our models include but are not limited to:
Phencyclidine (PCP) induced rodent models
Non-competitive NMDA receptor antagonists, such as ketamine, PCP or MK-801, are shown to produce complex symptoms that mimic positive and negative symptoms, as well as the cognitive deficits of schizophrenia. Given that it is well established that schizophrenia is associated with dopaminergic abnormalities, Creative Animodel establishes schizophrenia models by administration of the dopamine-releasing drug, d-amphetamine in combination with the open channel NMDA receptor blocker PCP.
The MAM model
The general consensus is that MAM administration at or before gestational day (GD) 15 produces too widespread a disruption of brain morphology and behavior to provide a useful model of changes seen in schizophrenia and that GD17 MAM is the optimal strategy. The MAM model appears to have reasonable face validity for positive and cognitive symptoms, and has construct validity in terms of structural and dopaminergic changes observed.
Model Characteristics and Pharmacology Evaluation
• Behavior measurement:
Cognitive tests: impaired acquisition of the T-maze delayed alternation, Morris water maze (MWM), novel object recognition (NOR) test
Sensorimotor assessment: prepulse inhibition (PPI), open field test
Social interaction tests
• Whole brain cerebellar and hippocampal volume measured by high-field MRI.
• The behavioral characteristics of models include post-pubertal onset, loss of hippocampal and cortical connectivity and function, limbic dopamine dysregulation, cortical glutamatergic hypofunction, vulnerability to stress, abnormal response to reward, social withdrawal and cognitive impairment.
Depression Models at Creative Animodel
Popular models of depression are widely used in the antidepressant drug discovery, such as stress exposure model, chronic unpredictable mild stress model (CUMS), maternal deprivation model, sleep deprivation model, social defeat. Creative Animodel will choose the ideal animal model for customers according to specific need. We perform all of those models with caution to provide insight into the etiology and the mechanisms underlying some symptoms of the major depressive disorder.
Chronic unpredictable mild stress model
CUMS paradigms aim to model a chronic depressive-like state that develops gradually over time in response to stress and is thus considered more naturalistic in the induction. Rats or mice are exposed to a series of different stress conditions over a period of several weeks. Several stressors (6–8) are applied (1 or 2 per day) for several hours each day. Typical stressors include overnight illumination, periods of food or water restriction, cage tilt, and isolation or crowded housing.
Social defeat model
The phenotypic trait produced in social defeat model is social avoidance, which can be quantified and is suggested to model social withdrawal in human depression. Conducting social defeat model, social conflict is created between male animals. This can be done by introducing an intruder animal into the home cage of another resident. The experiments are generally designed taking into account factors such as strain, body weight, and social status to ensure an outcome in which a defeated animal is produced.
Maternal deprivation model
A number of maternal deprivation paradigms exist that utilize repeated periods of separation of pre-weanling rats from the mother. Maternal deprivation model is suggested to have face validity for disrupted parenting behavior in humans that can result from a number of situations, including parental depression, also likely to occur during critical periods of development.
Sleep deprivation model
The diagnosis of depressive episodes is made when patients display a certain number of vaguely defined clinical symptoms for a 2-week period, such as sleep changes. Animals that are helpless in sleep deprivation model also show several features that are consistent with human depression.
A useful test will provide an end-point behavioral or physiological measure (read-out) designed to assess the effect of depression. There are many test methods available, such as forced swimming test, tail suspension test, and open filed.
Anxiety is affecting one-eighth of the total population of the world and has become a very important area of research in neurology. Physical symptoms of anxiety disorders are due to released stress hormones like adrenaline and cortisol, which have an effect on almost every organ in the body. Untreated anxiety disorders can lead to depression and strongly impede the daily life of patients, resulting in increased blood pressure, heart palpitations, chest pain, rapid breathing or breathlessness, sweating, increased muscle tension or irritability and decreased intestinal blood flow.
Being anxious, like feeling worried or fear, is an adaptive response to an unfamiliar environment, especially when confronted with danger or threat. Animal models can be used to contribute to understanding the information about molecular mechanisms involved in anxiety. Creative Animodel has developed various anxiety models for our customers to screen and develop new drug candidates.
Quite accurately mimic some symptoms found in human anxiety disordersRely heavily on discovering and validating more endophenotypesA number of behavioral tests to get valid dataCreative Animodel has spent years of hard work in developing anxiety models to help our customers. We provide not only high-quality animal models and tests but also a lot of information about the results. If you have any additional questions, please feel free to contact us for further details.
Epilepsy, characterized by recurrent seizures, is a chronic neurological condition including both partial epilepsies and generalized epilepsy. Partial epilepsies have a defined, focal region of seizure onset, though generalization to other brain regions may occur secondarily. There is a particularly high correlation between depression and complex partial seizures, which feature impaired consciousness and may often be characterized by motor automatisms. Temporal lobe epilepsy (TLE), a complex partial epilepsy affecting the temporal lobe region of the brain, is the most common form of epilepsy in humans. Generalized epilepsy involves multiple brain regions and is characterized by either tonic/clonic motor convulsions or brief losses of consciousness.
Our advantagesA relatively simple setup to finish the whole stable modelVarious animal models to mimic different types of human epilepsyCost-effective and rapid transgenesis to discover many variants
Creative Animodel is dedicated to exploring the validity of epilepsy. We provide stable animal models and excellent services to meet your specific needs. If you have any additional questions, please feel free to contact us for further details.
Experimental Autoimmune Neuritis (EAN) Models
Experimental autoimmune neuritis (EAN) models are reproducible models of auto-allergic demyelinating diseases of peripheral neurons tissue respectively, mainly served as an animal model for human Guillain-Barré syndrome (GBS).
GBS is a rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system. The estimated annual incidence in the United States is 1.65 to 1.79 per 100,000 persons. The initial symptoms are typically changes in sensation or pain along with muscle weakness, beginning in the feet and hands. During the acute phase, the disorder can be life-threatening.
GBS is believed to result from an aberrant immune response that attacks nerve tissue. Similarities in the pathology between GBS and the animal model of EAN indicate that EAN is an available object to investigate the mechanism of GBS and evaluate the novel drug which can cure GBS.
EAN Models at Creative Animodel
EAN models can provide valuable information regarding immune mechanisms contributing to inflammatory neuropathies, such as identification of neuritogenic epitopes, mechanisms involved in antigen recognition, the role of costimulatory signals, adhesion molecules, and various cytokines, as well as mechanisms of injury.
At Creative Animodel, we offer the EAN models establishment, as well as novel drug evaluation based on these models.
Creative Animodel has an expert team that has plenty of experience in experimental autoimmune neuritis model research. Our scientists would work closely with you on every step to help choose and design the most appropriate research plan. Looking forward to cooperating with you in the near future.
Creative Animodel is specialized in providing an integrated portfolio of thrombosis models to improve the molecular understanding and treatment of thrombosis. With cutting-edge facilities and technologies, we have strong expertise in developing disease models suited for testing disease-modifying compounds or drugs. What’s more, customized thrombosis models can be designed and developed on your demand.
What Is Thrombosis?
Thrombosis is the formation process of a blood clot (also called a thrombus) within the blood vessel. The clot can hinder the flow of blood in the affected area, and even cause serious complications when the clot transfers to a vital part of the circulatory system, like the brain or the lungs. The body produces platelets and fibrin to form a blood clot as a result of an injured blood vessel or certain conditions. Thrombosis is typically linked to cancer, trauma and surgery. Furthermore, hypoxia and embolization are two common complications of thrombosis.
Thrombosis can be divided into venous thrombosis and arterial thrombosis based on the location of thrombus. Arterial thrombus typically consists of platelet aggregates (known as white thombus), while venous thrombus is mainly composed of fibrin and red blood cells (known as red thrombus).
How to Establish Thrombosis Models?
Hypercoagulability, endothelial cell injury and disturbed blood flow are the main mechanisms of thrombosis formation, which provides information on how to develop thrombosis models to meet researches on pathogenesis, prevention and treatment. Thus, thrombosis models in laboratory are developed via mechanical disruption, photochemical injury, and ferric chloride (FeCl3) induction. Among these experimental approaches, FeCl3 is the most commonly used one to induce thrombosis and has made valuable contributions to the molecular understanding and treatment of thrombosis.
Our Thrombosis Models
We provide a comprehensive portfolio of thrombosis models dedicated to covering various types of thrombosis.
• Ferric chloride models
C57BL/6 mice or genetically engineered mice are anesthetized and a thrombus is induced by applying a solution of ferric chloride to the adventitial surface of the carotid artery or the femoral vein to develop arterial or venous thrombosis models respectively.
• Photochemical models
Rose Bengal has been proven particularly effective to induce vascular injury leading to thrombosis. Rodents are anesthetized and a 540-nm green laser light is trained on the surgically exposed common carotid artery from a distance of 5 cm. Rose Bengal is then injected to induce occlusive thrombosis.
• Mechanical injury models
We provide various mechanical injury models for your research, including ligation, stenosis and electrolytic models. The ligation models develop thrombi in the absence of blood flow, while the other two models develop thrombi in the presence of blood flow.
Model Characteristics and Evaluation
The primary endpoint of time to complete occlusion, in-life evaluation of blood flow, Doppler flow, and Thrombolysis in Myocardial Infarction (TIMI) blood flow scores.
• Various thrombosis models that fit for your research.
• A combination of thrombus formation techniques with transgenic technology provides a better understanding
of gene function.
• Integrated technical platforms, including real-time intravital microscopy and high-speed digital imaging, are
able to monitor and demonstrate the thrombus formation process.
• Comprehensive parameters are contained in our data report.
• Efficacy testing service are available based on your demand.
Creative Animodel, as a preclinical Contract Research Organization (CRO), has spent decades of efforts to provide specialty pharmacology services in human diseases. Our state-of-the-art facility and profound pharmaceutical knowledge enhance our capabilities to optimize and exploit disease models to advance the pharmaceutical industries.
Creative Animodel is specialized in providing an integrated portfolio of leukemia models to improve the molecular understanding and treatment of leukemia. With advanced facilities and technologies, we have strong expertise in developing disease models suited for testing disease-modifying compounds or drugs. What’s more, customized leukemia models can be designed and ordered on your demand.
The Severe Challenge from Leukemia
Leukemia is a group of cancers that commonly begins in the bone marrow and results in numerous abnormal white blood cells. The common symptoms of leukemia may include feeling tired, fever, pain in the bone or joints, increased the risk for infections, bleeding and bruising problems. Leukemia can bring about significant morbidity and mortality. In 2015, 2.3 million people were diagnosed with leukemia and 353,500 people died from it. Four types of leukemias account for 85% deaths from leukemias, which are acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL).
Until now, there is no effective way to prevent leukemia. The treatment of leukemia can be complex, likely involving chemotherapy, radiation therapy, targeted therapy, and bone narrow transplant. According to statistical data from SEER 18 2007-2013, approximately 60.6% people survive more than 5 years after being diagnosed with leukemia. Faced the severe challenge from leukemia, scientists are striving to better understand the underlying mechanisms and cure patients suffering from leukemia.
Our Featured Leukemia Models
To better comprehend leukemia and ultimately treat patients diagnosed with the disease, Creative Animodel strives to develop the most advanced and instructive leukemia models. The stringent model validation and quality control are necessary to ensure the reliability of the models for efficacy testing. Leukemia models are established via genetic fingerprinting, consistent tumor growth monitoring and other strategies.
We offer diverse immunocompromised models with varying genetic backgrounds and treatment histories for analyzing the effectiveness of drug candidates to treat leukemia, such as NSGTM-SGM3, the most effective engrafts in human leukemia researches.
We develop leukemia transgenic models via manipulation of embryonic stem (ES) cells (microinjection or electroporation), cre recombinase (in a tissue-specific manner) and other techniques to improve the understanding of leukemia at genetic level. The customized transgenic models are developed on your demand.
Creative Animodel, as a preclinical Contract Research Organization (CRO), has spent decades of efforts to provide specialty pharmacology services in human diseases. Our state-of-the-art facility and specialized knowledge enhance our capabilities to optimize and exploit disease models to advance the pharmaceutical industries.
Creative Animodel is an ideal partner in in vivo pharmacology research during the drug discovery and development process. With the state-of-the-art facilities and technologies, we have strong expertise in developing disease models suited for testing disease-modifying compounds or drugs. We currently provide comprehensive anemia models to improve the molecular understanding and treatment of anemia.
Anemia is a prevalent condition in which the amounts of red blood cells or hemoglobin are reduced, or the blood ability to carry oxygen decreases. The symptoms of anemia may include fatigue, weakness, pale or yellowish skin, shortness of breath, cold hands and feet, headache, dizziness, varying with the specific type of anemia. Anemia can affect anyone, but is most commonly found in women, children, and the elderly.
Types of Anemia
There are a variety of causes for anemia, which can be categorized into three types: blood loss, decreased red blood cell (RBC) production, and increased RBC breakdown. While iron or vitamin B12 deficiency, thalassemia, and neoplasms of the bone marrow result in decreased RBC production, genetic factors, infections, and certain autoimmune diseases result in increased RBC breakdown. Consequently, anemia can be classified into multiple types, such as aplastic anemia, vitamin B12 deficiency anemia, folic acid deficiency anemia, thalassemia, sickle cell anemia, paroxysmal nocturnal hemoglobinuria, etc. based on causes.
Based on BRC indices, anemia can also be divided into microcytic anemia, macrocytic anemia, hypochromic anemia, and normocytic anemia. Normocytic anemia is further divided into aplastic anemia, hemolytic anemia, acute posthemorrhagic anemia and other types of anemia. RBC indices that help diagnose the cause of anemia, include average red blood cell size (MCV), hemoglobin amount per red blood cell (MCH) and the amount of hemoglobin relative to the size of the cell (hemoglobin concentration) per red blood cell (MCHC).
Anemia Models at Creative Animodel
Creative Animodel is specialized in establishing a variety of anemia models that cover almost all types of anemia for preclinical testing. We apply the following methods to mimic anemia on mice or animal species you asked.
• Chemical induction
Phenylhydrazine (PHZ) is an effective chemical to induce hemolytic anemia in mice. Benzene injection in mice can mimic anemia of bone marrow suppression induced by chemotherapy. Other chemicals, like busulfan and chloramphenicol can be also used to cause bone marrow failure.
• Blood loss
Both tail bleeding and hemospasia via veins are useful methods to develop blood loss anemia and anemia of inflammation.
• Nutritional deficient diet
Iron-deficient diet can successfully cause iron deficiency anemia in mice, and folate or vitamin B12 deficient diet can induce folic acid deficiency anemia.
• Inbred strains
We provide excellent NZB and NZW inbred mice strains for the pharmacological research on autoimmune hemolytic anemia.
• Transgenic technology
Transgenic technology can be used to alter the expression level of gene of interest or delete gene to induce a condition similar to anemia. For example, overproduction of IL-6-hepcidin-ferroportin can cause a condition similar to anemia of inflammation. Other anemia, like Fanconi anemia, thalassemia, paroxysmal nocturnal hemoglobinuria, and sickle cell anemia, can also be successfully induced in mice with our transgenic technologies. More customized anemia models are available to satisfy your specific research.
Creative Animodel has spent decades of efforts to provide specialty pharmacology services in human diseases. Our state-of-the-art facilities and profound pharmaceutical knowledge enhance our capabilities to optimize and exploit disease models to advance the pharmaceutical industries. We sincerely wish to discuss with you in a further step.
Diabetic Retinopathy Models
Creative Animodel provides non-human primate models (NHP) of diabetic retinopathy (DR) to conduct pre-clinical drug screening, efficacy & safety assessment, and fundamental studies. The NHP model is the highest transnational models for novel drug development for which replicates the human ophthalmic pathologies including retinal thickening, hemorrhage, cyst and fluid, morphological changes of vessels, optic nerve, etc.
What Is Diabetic Retinopathy?
DR, a major complication of diabetes mellitus, is one of the leading causes of blindness worldwide. Early diagnosis and prevention of retinopathy in diabetic individuals is crucial for preventing vision loss. There are more than 300 million people suﬀering from diabetes, and is expected to affect an estimated 500 million by 2030. Prolonged hyperglycemia causes irreversible pathological changes in the retina, leading to proliferative DR with retinal neovascularization and diabetic macular edema (DME) in some individuals. Studies have shown that nearly all individuals with type 1 diabetes and more than 60% of individuals with type 2 diabetes have some degree of retinopathy after 20 years. Clinically, DR can be classified into non-proliferative DR (NPDR) (Fig. 1A) and proliferative DR (PDR) (Fig. 1B). Current studies suggest that approximately one-third of the diabetic population have signs of DR and about one-tenth have vision-threatening stages of retinopathy, including PDR and DME.
Fig. 1. Clinical features of DR.
Treatment of DR can be achieved through an enhanced understanding of disease pathogenesis. However, because most structural, functional and biochemical studies cannot be carried out in human subjects, animal models are essential for studying DR pathology, and thus for developing new and better treatments.
Our Non-human Primate Models of Diabetic Retinopathy
The structural similarity of primate eyes to human eyes makes them potential models for research on eye diseases. The studies of DR in monkey at Creative Animodel can be divided into two groups: type 1 diabetic model and type 2 diabetic model.
• Type 1 diabetic model
Spontaneous or pharmacological induction of hypertension in the hyperglycemic monkeys results in ischemic retinopathies, such as cotton-wool spots which are found in the peripapillary region, microaneurysms, capillary dropout, capillary dilatation, etc.
• Type 2 diabetic model
DR studies have also been carried out on monkeys that spontaneously develop type 2 diabetes. Our type 2 diabetic primate models can reveal hemorrhages, large areas of retinal capillary non-perfusion, microaneurysms, cotton wool spots, intraretinal hemorrhages and hard exudates in the macula.
Our Imaging Capability
Optical coherence tomography (OCT) and fundus photography (FP) are the most important tools in ophthalmology. Creative Animodel has extensive OCT and FP experience for ophthalmology study to help conduct pre-clinical drug screening and efficacy & safety assessment.
• OCT—focusing on retinal thickness, drusen, cyst and fluid
• Retinal thickness analysis: point counting and thickness map
• FP—focusing on retinal exudate, hemorrhage, morphological changes of vessels and optic nerve by SIVA software
Creative Animodel will keep close communication and coordination with you during the period of both model establishment and drug assessment. Therefore, we could be the best partner for your research to understand the pathogenesis of diseases in human, defining novel therapeutic targets as well as screening of novel therapeutic drugs. If you have any questions, please don’t hesitate to contact us.
Creative Animodel is an ideal partner in in vivo pharmacology research during the drug discovery and development process. With the state-of-the-art facilities and technologies, we provide non-human primate models of glaucoma to conduct preclinical drug discovery, efficacy and safety assessment, as well as fundamental studies.
What Is Glaucoma?
Worldwide, glaucoma is a leading cause of irreversible blindness and visual field defects. It is estimated that the disease will affect over 80 million people by 2020. Glaucoma is not one single disease entity
Non-human Primate Models of Glaucoma
The discovery of therapeutic drug targets relies heavily on animal models which represent a valuable tool for understanding both the progression and cause of human diseases. Creative Animodel has developed non-human primate models of glaucoma for the study of the pathophysiology of human glaucoma and drug discovery. Our animal models are characterized by low cost, reproducibility, easy disease-induction and limited side effects to neighboring tissue. Our glaucoma models include:
• Primary Open Angle Glaucoma (POAG) models
POAG is characterized by elevated IOP, acquired loss of RGCs and atrophy of the ON. We use argon laser photocoagulation which results in IOP elevation in 70% of the animals. Histopathologic specimens from eyes with elevated IOP and ON cupping show selective loss of RGCs and thinning of the nerve fiber layer compared with specimens from untreated controls suggesting that glaucoma is achieved.
• Other experimental models of IOP elevation
Our monkey models of chronic IOP elevation are developed by using latex microspheres or autologous fixed red blood cells. We also establish acute elevation of IOP which can be used to study the mechanism of ON damage.
Advantages of Non-human Primate Models
• Have close relative and high homology with humans;
• Own almost identical cetinal and ON anatomy like humans’;
• Improve clinical indicators of initial optic nerve damages in glaucoma broadly.
Creative Animodel has spent decades of efforts to provide professional pharmacology services in human diseases. We are your best partner for your research to understand the pathogenesis of diseases in human, define novel therapeutic targets as well as screen novel therapeutic drugs. If you have any questions, please don’t hesitate to contact us.
Creative Animodel offers extensive portfolio of both in vitro and in vivo services in pharmacology and toxicology. With rich-experienced scientists and state-of-art technique platforms, we can provide various cataract models to determine the effectiveness of anti-cataract therapies and a stronger scientific rationale for testing these therapies in human patients for our customers.
Overview of Cataract
There are an estimated 50 million blind people in the world, and cataracts (opacities of the lens in the eye) are responsible for half of these cases. The main risk factors associated with cataract are predominantly aging and diabetes, while others include nutrition (malnutrition and obesity), exposure to sunlight, genetics, gender, smoking and alcohol. Currently, the only way to treat cataracts is surgery. However, with an aging population, the demand of surgery and the need of cost-effective alternative solutions grows. It has been predicted that delaying the onset of cataract by ten years will halve its incidence. But developing anti-cataract strategies using human donor lenses is fraught with difficulties. Barriers to this include the limited availability of human donor lenses and intact cataractous lenses, the narrow age range (since lenses are typically from older donors), post-mortem delay between death and tissue processing and the inherent variability between donors (genetic variation, systemic disease, cause of death and exposure to environmental risk factors). While not ideal, this has led investigators to turn to animal models of lens cataract.
Our Cataract Models
Animal models have been used to either study the pathogenesis of cataract, or to test anti-cataract therapies with a long-term view to reduce the incidence of cataract in humans. With the state-of-the-art facilities and technologies, Creative Animodel can select the most appropriate models for our customers to determine the effectiveness of anti-cataract therapies and provide a stronger scientific rationale for testing these therapies in human patients.
Mice, rats, rabbits, pigs and non-human primates are used to establish cataract models at Creative Animodel. Our cataract models can be classified into three groups: inducible cataract models, hereditary models and knockout animal models.
• Induced cataract models
Lens cataract models are induced in rodents by the administration of a wide variety of chemical agents, exposing to UV radiation or the generation of nutritional deficiencies. There are similarities of lens cataracts and other features between these inducible animals and human patients with ARN cataracts.
• Hereditary cataract models
The Emory mouse is useful genetic animal model for age-related cataracts. Two sub-strains of Emory mice exist in which cataracts develop at 5-6 months (early cataract strain) and 6-8 months (late cataract strain). These cataracts increase in severity with age and initially appear in the lens superficial cortex before progressing into the deep anterior cortex and ultimately to complete lens opacification.
• Knockout cataract models
Our knockout cataract models include glutaredoxin 2 (Grx2) knockout mouse and lens glutathione (GSH) synthesis knockout (LEGSKO) mice. Grx2 KO mouse is a good model to study human ARN cataract due to loss of GSH, increased protein-bound GSH (PSSG) accumulation and chaperone protein function. And the LEGSKO mouse can be used for the development of pharmacological anti-cataract agents that could restore the antioxidant reserve of the lens or block the effects of oxidative stress resulting from GSH deficiency.
Creative Animodel offers end-to-end validated pre-clinical models and related services of pharmacology and toxicology. We support the global clients in models establishment, imaging modalities, behavioral tests as well as biomarker endpoint assays to help identify novel therapies for cataract. Please feel free to contact us for more information.
Age-related Macular Degeneration Models
Creative Animodel provides age-related macular degeneration (AMD) models to conduct pre-clinical drug screening, treatment evaluations, as well as fundamental studies. Based on your research objectives and parameters, our experienced experts will establish the most suitable animal model to meet your needs.
What Is Age-related Macular Degeneration?
AMD is a progressive condition of the retinal pigment epithelium (RPE), its supporting basement membrane and the overlying photoreceptor layer. Among individuals older than 65, AMD is regarded as the leading cause of blindness in the industrialized world.
Our Non-human Primate Models of AMD
Accurate animal models of a disease can assist greatly in the development of new therapies. With extensive experience and advanced platforms, we provide non-human primate models of AMD to conduct pre-clinical drug screening, efficacy & safety assessment, and fundamental studies. Creative Animodel has both spontaneous dry AMD and laser-induced CNV models.
• Non-human primate models of spontaneous dry AMD
Non-human primates are the only animals with a retinal structure closely resembling that found in humans, most notably the presence of a macula. In the center of the macula, the central fovea has multiple features designed to optimize spatial resolution. In addition, blood vessels are absent from the inner retina and a central capillary-free zone. Furthermore, several non-human primate species develop the early to intermediate stages of AMD. Macular degeneration occurs in rhesus and cynomolgus macaques at Creative Animodel. In both, retinal lesions are characterized by drusen accumulation in the central retina.
• Non-human primate models of laser induced CNV
The use of laser injury to disrupt Bruch’s membrane and induce CNV has been developed in a non-human primate at Creative Animodel. The model can be used to demonstrate the safety and efficacy of the treatment. Typical argon laser exposure parameters for the induction of CNV have included a 50 um spot size, 100 ms duration and powers ranging from 300 to 700 mW. Outcome measures of efficacy include the extent of growth of laser-induced new vessels, the total area of blood vessel leakage and the percentage of laser lesions resulting in clinically significant (Grade III and IV) vessel leakage.
Creative Animodel is the best partner in pharmacological researches on drug discoveries and disease treatments. We can provide non-human primate models of AMD to conduct AMD treatment evaluations. Our high-quality image and reliable data further optimize drug development process accurately and efficiently. If you have any questions, please don’t hesitate to contact us.
Experimental Autoimmune Uveoretinitis (EAU) Models
Experimental autoimmune uveoretinitis (EAU) in rats and mice can imitate a prototypic T cell-mediated autoimmune disease that targets the neural retina and related tissues. The model is used to represent human sight-threatening inflammatory eye diseases that are believed to have an autoimmune etiology, and to study basic mechanisms of tolerance and autoimmunity to organ-specific antigens from immunologically privileged sites.
EAU model is an induced, as opposed to spontaneous, autoimmune disease model. It can be elicited by peripheral immunization with a number of purified retinal proteins or peptides derived from them (uveitogens) in adjuvant, or by adoptive transfer of lymphocytes specific to these antigens. The hallmarks of EAU are onset of ocular inflammation, disruption of the retinal architecture, and partial to complete destruction of the photoreceptor cell layer. The type, number, and size of lesions serve as a basis for a semiquantitative grading system used to score disease severity.
EAU Models at Creative Animodel
At Creative Animodel, we offer EAU models established on rats and mice by different induced agents. Novel drug evaluations are available based on these EAU models, but the choice of model will depend on the specific needs of the study.
The agents used to induce EAU in rats and mice:
Retinal-soluble antigen (S-Ag, arrestin)
This 48-kDa intracellular photoreceptor protein is involved in the phototransduction cascade. It binds to photoactivated-phosphorylated rhodopsin, thereby apparently preventing the transducin-mediated activation of phosphodiesterase. Immunization with 30 μg of S-Ag in complete Freund’s adjuvant (CFA) usually results in disease’s onset between days 12 and 14.Interphotoreceptor retinoid-binding protein (IRBP)
This 148-kDa protein is found in the interphotoreceptor matrix, and is thought to transport vitamin A derivatives between the photoreceptor and the retinal pigment epithelium (RPE). IRBP is composed of four homologous domains, which are thought to have arisen by gene duplication. Using as antigen 30 μg of peptide R16 of bovine IRBP, typically results in disease’s onset on day 9 or 10.Rhodopsin, and its illuminated form, opsin
This 40-kDa intracellular protein is the rod visual pigment. Pathoge¬nicity of this protein appears to be conformation-dependent, as rhodopsin is more pathogenic than opsin. Immunization with microgram quantities of a uveitogenic protein or peptide in complete Freund's adjuvant (CFA) can induce disease that within a period of days or weeks results in disruption of the retinal architecture and complete destruction of the photoreceptor cell layer.
Creative Animodel has rich experience in establishment of experimental autoimmune uveoretinitis models. And we can also provide the comprehensive evaluation for your new drugs. Our scientists will help clients choose and design the most appropriate research plan. If you have any questions, please don't hesitate to contact us.
Rheumatoid Arthritis Models
Rheumatoid Arthritis (RA) is a chronic, autoimmune disease in which the body’s immune system mistakenly attacks the joints. This creates chronic inflammation and causes a thickened synovium, swelling and pain around the joints. RA has been a burden to patients since it could lead to pain, disability, and even worse results. It could also affect other parts of the human body including eyes, mouth or lungs.
While the cause of RA is not clear yet, it is certain that RA affects plenty of people all over the world. About 0.5 to 1% of adults in the developed world has RA. In the United States, there are 1.5 million people suffering from the disease. The number of women who have RA is three times more than the man’s. Additionally, middle-aged people around 30-60 years old are more frequent to be affected. RA will cause a series problem threatening people’s health and life.
Rheumatoid Arthritis Models at Creative Animodel
We offer the most comprehensive preclinical animal testing services for rheumatoid arthritis, which range from animal models’ establishment to lead drug candidates’ toxicity and efficacy evolutions in various species.
Non-human primate (NHP) rheumatoid arthritis models are extremely difficult to generate because of the low and inconsistent incidence in monkeys. To solve this issue, scientists at Creative Animodel experimented type II collagen induced arthritis in Cynomolgus monkeys, and successfully established a reliable NHP arthritis model that can be used in rheumatology studies, and inflammation related anemia or pain studies.
Collagen-induced arthritis (CIA) model
Among the different animal models, collagen-induced arthritis (CIA) mouse model is the most popular and commonly used model. CIA model is induced by immunization with heterologous type II collagen in complete Freund's adjuvant (CFA). CIA shows the same clinical, histological and immunological features with the human rheumatoid arthritis including an increase of pro-inflammatory cytokines such as TNF-α, IL-6, erosion of bones, and pannus formation.
Collagen antibody-induced arthritis (CAIA) model
Collagen antibody-induced arthritis (CAIA) is a simple and synchronized alternative to the CIA model. The advantages of CAIA model compared to the CIA model are that CAIA model has rapid disease onset (24 to 48 hours), high uptake rate, synchronicity and lack of influence of Freund’s adjuvant. Therefore, this model is perfect for investigating the pathological role of individual gene products, pro-inflammatory and anti-inflammatory cytokines, screening and evaluating anti-inflammatory agents.
Adjuvant-induced arthritis (AIA) model
Adjuvant-induced arthritis (AIA) model is known for its reliability and well-understanding. It is mostly used for evaluating potential treatment of RA and other preclinical or clinical investigations.
Sepsis is a state of disrupted inflammatory homeostasis that is often initiated by infection. It represents a very severe reaction of the immune system, activation of the pro-inflammatory cascades and the compensatory anti-inflammatory response. The resulting hemodynamic changes, microcirculatory disturbances and cellular disorders create a disparity between tissue perfusion and metabolic demands. The development and progression of sepsis is multi-factorial, and affects the cardiovascular, immunological and endocrine systems of the body. The complexity of sepsis makes the clinical sepsis study and sepsis therapeutics difficult.
Sepsis Models in Creative Animodel
Creative Animodel has successfully established some robust and reproducible sepsis animal models. Based on those models, we provide a set of preclinical services to evaluate the efficacy and safety of your drug candidates.
• LPS-induced Sepsis Model
Endotoxin or lipopolysaccharide (LPS), the principal component of the out membrane of Gram (-) bacteria, can stimulate the release of inflammatory mediators from various cell types, responsible for initiating the process of sepsis, including increase of pro-inflammatory cytokines, such as TNF-α, IL-1, IL-6 and IL-8. This model is highly reproducible, easy to monitor by a variety of endpoints, and closely mimics clinical sepsis.
• CLP-induced Sepsis Model
The most widely used sepsis model is achieved by cecal ligation and puncture (CLP) which is recognized as one of the models with the greatest compatibility in clinical terms. With this sepsis model, the peritoneum is contaminated with mixed flora in the presence of devitalized tissue. This model, which can demonstrate apparent similarity to the clinical situation in perforated appendicitis or diverticulitis, is a robust and reproducible preclinical model of poly-microbial sepsis to facilitate drug screening. It can be used in a variety of different types of studies including development of antibiotics, antithrombotics, immune modifiers, and diagnostics.
Our Pharmacology Evaluation
We provide a package of preclinical evaluations for your drug candidates based on our sepsis models, including but not limited to:
• White blood cell counts
• Blood and tissue collection and colony forming unit (CFU) determination
• Cytokine/chemokine analysis
• Serum biochemistry assays
• PK/PD analyses
Creative Animodel spares no effort to create reproducible animal models for studying sepsis pathogenesis and preliminary testing of potential therapeutic agents. We have a team of scientists with profound pharmaceutical knowledge to support you in all aspects of new drug discovery and development. If you have any question, please feel free to contact us.
Creative Animodel is a professional contract research organization offering kinase screening and profiling for kinases based drug discovery. With years of experience in kinase screening and profiling, we offer our clients professional and reliable information to accelerate the process of kinase drug discovery.
What Are Kinases?
A kinase is a kind of enzyme that catalyzes transfer of phosphate groups from high-energy, phosphate-donating molecules like ATP to specific substrates, and this process is called phosphorylation. Involving in cell signaling, metabolism, cellular transport, protein regulation and other cellular pathways, kinases are very important for human physiology. More than 500 different kinases are coded by human genome, which can be classified into seven groups. Kinase is one of the most important target families in drug discovery, and constantly treats as an popular area of interest of pharmaceutical industry and academia. Inhibitors of kinases can dampen hyperactive processes which would be important treatments for human diseases. It is reported that there are 30 kinase inhibitors approved by FDA, which increases interests of kinases as a drug target class.
Kinase Services at Creative Animodel
In order to understand structure/activity relationships, avoid targets with toxic liabilities and select satisfying drug candidates, it is essential to conduct a wild range of screening and profiling for new kinase inhibitors programs. We provide biochemical assays and cell-based assays for your kinase based drug discovery.
• Biochemical assays.
Biochemical assays include two classes: activity assays and binding assays. We can offer different kinase assay platforms based on clients’ needs, including radioisotope filter binding, scintillation proximity, fluorescence resonance energy transfer (FRET), time-resolved fluorescence resonance energy transfer (TR-FRET), luminescence detection, mobility shift and competition binding.
• Cell-based assays.
The cell-based data offers a more comprehensive view of biological context and resulting cellular responses, allowing for more informed decisions to be made about which compounds advance and which one need to be cut out. We provide a growing menu of homogenous, functional assays to detect activated kinases in whole cells, including activity evaluation services, compound binding assay, protein interaction detection, cellular selectivity screen and compound screening, etc.
• Nearly 500 kinases to help clients to conduct kinase screening and profiling for selectivity testing.
• Deliver reliable results in a rapid timeline to assist clients with getting data quickly.
• Use a cutting-edge compound management system to provide high-quality data for every project.
Creative Animodel is a leading contract research organization providing GPCRs services to meet the needs of drug discovery. Our experienced scientists and professional technical platforms enable us to deliver reliable results in a cost-efficient manner.
What Are GPCRs?
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors (GPLR) constitute a large protein family of receptors. GPCRs can detect molecules outside the cell, activate internal signal transduction pathways and cellular responses. They involve a wide range of physiological processes, such as visual sense, gustatory sense, sense of smell, regulation of immune system activity and inflammation, as well as autonomic nervous system transmission. Because of their important functions, they are associated with diseases ranging from cardiovascular diseases, autoimmune diseases, inflammation, cancer, and diseases of the nervous system. In addition, GPCRs are one of the most popular drug targets for the reason that they can be modulated by small molecules, peptides, and proteins. It is reported that about 40% of drugs on the market are targeting GPCRs. And GPCR screening and profiling plays an important role in GPCR drug discovery.
Creative Animodel has extraordinary experience in drug discovery targeting nuclear receptors. With years of expertise in this field, Creative Animodel is dedicated to providing high-quality services and reliable outcomes of nuclear receptor screening and profiling. We are confident in accelerating your experimental progress and achieving ideal research goals with the most competitive price.
What Are Nuclear Receptors?
Nuclear receptors (NRs) are a large superfamily within cells that are responsible for sensing thyroid hormones, steroid hormone, vitamin D, fatty acid, sterol oxide and certain other molecules. Nuclear receptors have two subtypes, steroid and non-steroid. When a ligand is present, activated nuclear receptors can directly bind to DNA and regulate the expression of specific genes to control the metabolism and development of organisms. Therefore, nuclear receptors can play a role in the pathology of cancer, inflammation, cardiovascular diseases, and reproduction. The unique characteristic of nuclear receptors differing from other receptors is their ability to up-regulate or down-regulate gene expression. This ability makes nuclear receptors involve therapeutic targets of various diseases.
Nuclear Receptor Assays at Creative Animodel
Creative Animodel offers a comprehensive service of cellular and biochemical nuclear receptor assays to profile your compounds. We have carried out a broad range of nuclear receptor binding and profiling assays, such as glucocorticoid receptor, progesterone receptor, androgen receptor, mineralocorticoid receptor, estrogen receptor, and retinoic acid receptor. Our nuclear receptor services include but are not limited to:
• Ligand binding activity
• Nuclear receptor translocation
• Nuclear receptor coregulator interaction
• High throughput screening
• IC50 determination and selectivity
Other than assays mentioned above, Creative Animodel has also developed customized assays for our clients. Our nuclear receptor experts can provide high-quality experimental design to evaluate the efficacy, potency, and selectivity of your compounds.
Creative Animodel provides a wide range of in vitro pharmacology services to help achieve your goals of drug research and development. All our services are conducted under GLP compliant. If you have any special needs in nuclear receptor assays, please don’t hesitate to contact us. We look forward to working together with you in the near future.
Creative Animodel is a global leader in in vitro drug screening and profiling with a comprehensive offering of services designed to shorten and simplify your drug discovery study. With rich-experienced scientists and state-of-the-art technique platforms, we can provide a broad portfolio of both binding and functional assays for ion channels.
Ion Channels in Diseases and Drug Discovery
An ion channel is a gated and water-filled pore created by transmembrane proteins to help establish and control voltage potential across cell membranes by controlling the active flow of ions between the intracellular and the extracellular environments. The ion channel family is intimately involved in almost all aspects of physiology and plays a critical role in diverse processes such as nerve and muscle relaxation, cognition, regulation of blood pressure, sensory transduction, and cell proliferation. Their modulation has been linked to a broad range of diseases that include cardiac disorders, kidney failure, neurological indications, the perception of pain, and blindness. Over 60 “channelopathies” have been identified as human diseases that are brought about through mutations in ion channels. Given the central functional role that the ion channel superfamily plays in human physiology, its membrane localization, and the diverse tissue distribution of different members of ion channels family, it represents an attractive potential target class for drug discovery.
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Ion Channel Screening & Profiling Services at Creative Animodel
Over ten years’ experience as an ion channel CRO has enabled us to better understand our customers' latent needs. Our scientific experts are ready to reduce the risk and maximize the success of your discovery programs. Our services include but are not limited to:
• Ion channel binding assays
Our binding assay utilizes the gold standard filtration method to produce highest assay robustness. Ion channel binding assays are conducted with membrane preparations produced in-house to control for the quality of these critical reagents and to ensure tight data reproducibility. Radioligand binding assays are a useful method for monitoring potential hERG liability at the earliest phase of drug discovery.
• Ion channel functional assays
Creative Animodel provides a wide range of functional assay services, including flux-based assays, manual patch clamp assays, fluorescence-based assays, automated electrophysiological assays and microelectrode array assays. From single-cell manual patch clamp to high throughput 384-well automated electrophysiology instruments, we use our cells on several different platforms to provide the throughput or depth of analysis that meet your demands.
• Human cardiomyocytes cardiotoxicity services
Cardiotoxicity is a major cause of drug development failure and withdrawals. The human ether-a-go-go related gene (hERG) screening alone can’t reliably detect potential cardiac adverse side effects. To better predict proarrhythmic risks using in vitro assays, a comprehensive in vitro proarrhythmia assay (CiPA) has been proposed. Creative Animodel provides complimentary approaches, including Multiple Electrode Array (MEA), High Content Analysis (HCA) and manual patch clamp assays, to reliably detect and characterize cardiac safety risks.
Creative Animodel can provide our customers the comprehensive services and highest quality results of ion channel screening & profiling assays. With the help of our talented scientists, we are confident in accelerating your project progress and achieving ideal research goals with the most competitive price. If you have any special requirements, please feel free to contact us. We look forward to working together on your attractive projects.
The National Cancer Institute (NCI) has defined the cardiotoxicity as “toxicity that affects the heart”. With the advent of pharmaceuticals for conditions such as cancer, cardiotoxicity characterized by abnormality of cardiac electrical activity and contractile dysfunction has often been observed. Cardiotoxicity of drugs includes a direct damage to the heart and indirect effects because of the enhancement of haemodynamic flow alterations or thrombotic events. Drug-induced cardiotoxicity can be divided into 3 parts at the molecular level, including direct damage to mitochondria, disruption of kinase signaling pathways, and inhibition of cardiac ion channels. Adverse cardiac effects are the main reason for drug discontinuation and failure of clinical trials. It is reported that cardiotoxicity is responsible for 40% of drugs withdrawn between 1994 and 2006. What’s more, about 10% of drugs have been recalled from the market owing to cardiovascular concerns in the last four decades. Therefore, information obtained from cardiotoxicity is essential for the drug development. The early and efficient assessment of cardiac safety plays a significant role to confidently accelerate novel drug development.
Available Cardiotoxicity Services
Preclinical cardiotoxicity screening should be carried out to detect unsafe compounds sufficiently early in the drug discovery process to help make right decisions about candidate drug selection, reduce late-stage attrition, as well as save time and costs. Creative Animodel provides reliable and professional assays for cardiotoxicity.
Microelectrode Array Cardiotoxicity AssayshERG InhibitionCardiac ChannelsAction Potential DurationQT Prolongation AssayArrhythmogenic Liability Screening Comprehensive in Vitro Proarrhythmia Assay (CiPA)3D Cardiotoxicity Assay
Our AdvantagesProfessional assay platforms to offer reliable dataHuman pluripotent stem cell-derived cardiomyocytes available Diverse approaches to detect and characterize cardiac safely risksAssays conducted according to regulatory guidances
With years of experience, Creative Animodel offers a wide range of toxicology and safety pharmacology assays for the early stage of drug discovery and development. Our cardiotoxicity services provide clients high-quality data to detect cardiac risk and support drug discovery in a cost-effective and time-saving manner. If you have any questions or specific needs, please feel free to contact us.
hERG stands for the human ether-à-go-go-related gene. It can code for a protein (Kv11.1) which is the alpha subunit of a potassium ion channel. This ion channel simply, called as hERG channel, can affect the electrical activity of the heart that coordinates the beating of the heat. When the ability of this hERG channel to conduct electrical current across the cell membrane is inhibited or compromised, it can lead to QT interval prolongation resulting in potentially fatal ventricular tachyarrhythmia called Torsade de Pointes (TdP). Many drugs have been withdrawn from clinical trials because of the cardiotoxic effects. The compounds exhibiting cardiotoxicity related to hERG inhibition in vivo will be identified by in vitro hERG inhibition assays, which is a highly sensitive measurement. Meanwhile, U.S. Food and Drug Administration (FDA) has made hERG safety testing mandatory. Therefore, it is important to identify inhibitors early in the drug discovery.
hERG Safety Assay at Creative Animodel
With comprehensive expertise and state-of-the-art technologies, Creative Animodel performs assays to screen candidate compounds for hERG safety during the preclinical stage, which can benefit the decision-making of your drug discovery and development. Methods. The advanced automated patch clamp system are used to provide a higher-throughput hERG safety assay. In addition, the manual patch clamp electrophysiology measurement is available to achieve high accuracy without compromising data quality. We can choose the appropriate methods depending on clients’ needs. Cell lines. All assays are conducted by using stable cell lines, such as CHO-hERG cells, HEK293-hERG cells, etc.Deliverables. Our reports include protocol summary, IC50 (concentration at which 50% inhibition is observed), channel inhibition rate, etc.
Creative Animodel has years of experience in professional toxicology services. As your trustworthy partner, comprehensive assessments of cardiotoxicity are available and we conduct assays in compliance with the requirements of regulatory agencies, like FDA and EMA. In addition, we can offer high-quality hERG safety assay with a rapid turnover time to you in a cost-effective manner. If you have any questions or specific requirements, please feel free to contact us.
Cardiac Action Potential Duration
The cardiac action potential is a presentation of the change in voltage (membrane potential) across the cell membrane of heart cells. Unlike action potential found in other types of electrically excitable cells, the cardiac action potential is not initiated by nervous activity but arises from a group of specialized cells that can generate automatic action potential generation. The cardiac action potential can be recorded to produce an electrocardiogram (ECG), which is a series of upward and downward spikes (labelled P, Q, R, S, and T). Action potential duration (APD) means the duration of the action potential, typically measured at 50% or 90% of full repolarization, relative to the peak amplitude of the action potential. In normal cardiac myocytes, the APD is several hundred milliseconds. The ADP determines the refractory period of the heart. If ADP becomes short, it can cause premature re-excitation, which leads to arrhythmogenic phenomena as re-entry. On the other hand, the APD’s prolongation is also dangerous. It can cause early after-depolarizations and arrhythmias seen on the ECG as ‘torsades de pointes’ (TdP). Therefore, it is important that the cardiac APD is regulated precisely.
Cardiac Action Potential Duration Assays at Creative Animodel
Cardiac action potential duration assays are recommended for investigational new drug (IND) submissions. At Creative Animodel, we provide reliable cardiac APD assays with human cardiomyocytes or Purkinje fibers.Action potential duration with human cardiomyocytes.
Creative Animodel has developed a proven cellular model with manual patch clamp recordings of action potentials in isolated induced pluripotent stem cell-derived human cardiomyocytes (SC-hCMs). SC-hCMs have the intrinsic pacemaker activity, which leads to spontaneous action potential firing. And it makes possible to determine the effect of a test compound on action potential firing frequency and to identify compounds with the potential to slow (bradycardia) or increase (tachycardia) heart rate. Therefore, APD assay with SC-hCMs is a useful tool to obtain the influence of test compounds on action potential prolongation and arrhythmia.Action potential duration with Purkinje fibers.
Creative Animodel offers physiologically relevant assessment of drug effects on APD. Purkinje fibers are regarded as an important site of for initiation of arrhythmias. The intracellular recordings of action potentials in animals’ Purkinje fibers are used to evaluate paced electrical response for detection of drug-induced action potential prolongation and arrhythmia.
With years of experience, Creative Animodel has successfully conducted many experiments about cardiotoxicity for our global clients. As your reliable partner, we can offer high-quality cardiac action potential duration assays based on expertise in cardiac safety pharmacology. In addition, assays in canine, guinea pig atrial or ventricular myocytes are also provided depending on clients’ requests. If you have any questions or specific requirements, please feel free to contact us.
Neuronal Signaling Assays
Neurons are the cornerstone of complex neural networks. The neuronal signaling is a kind of electrical signaling of which electrochemical changes occur sequentially on nerve fibers. When the nerve is stimulated, the permeability of the neuron membrane drastically changes with a mass of influx of Na+ and outflow of K+.
It is shown that electric potential changes when signaling is transmitted in the neuron, while synaptic signaling occurs when the signal is transmitted across the synaptic cleft between neurons through the action of neurotransmitters. Neurotransmitters such as dopamine, glutamate and γ-aminobutyric acid (GABA) are stored in synaptic vesicles of presynaptic neurons. The vesicles fuse to the presynaptic membrane and release the neurotransmitters into the synaptic cleft after receiving appropriate signal. Some neurotransmitters then bind to receptors on the postsynaptic membrane. Receptor families, such as the dopamine receptors, can signal through adenylate cyclase to activate signaling intermediates. Activated signaling intermediates then regulate gene expression through the actions of CREB and other transcription factors. Other neurotransmitters bind ion channels such as NMDAR or AMPAR that regulate flux of Ca2+ and Na+, thereby extending the action potential via postsynaptic neurons.
Neural Crest Cell Migration Assays
Neural crest cells are a group of transitional pluripotent cells during embryonic development. They can be induced to migrate and differentiate into various cell lineages, such as melanocytes, craniofacial cells, chondrocytes, osteocytes, smooth muscle cells, central or peripheral neurons, and glial cells. Neural crest cells originate in the dorsal neural folds and initiates migration shortly after closure of the neural tube. Neural crest cells first begin migrating in the cranial region, occurring in an anteroposterior direction along the neural axis. During their migration, neural crest cells come into contact with the neural tube and the somites. In the trunk region of the embryo, neural crest cells have classically been thought to follow two primary migratory pathways: (a) a dorsolateral pathway, under the ectoderm; (b) a ventral pathway, between the neural tube and the somites.
Neural crest cells arise at the time of neurulation and migrate to their target sites in the body, where they give rise to very different cell types. When the regulated processes of neural crest cell development and migration are altered, dramatic pathological consequences, called neurocristopathies, can be the result. For example, failure of the neural crest cells to colonize the gut leads to incomplete innervation of the gastrointestinal tract, which results in Hirschsprung’s disease. A diminished number of neural crest cells migrating to the cranial structures leads to Treacher-Collins syndrome. Therefore, defining the molecular mechanisms of neural crest cell migration is important for our knowledge of human disease.
Neural Crest Cell Migration Assays at Creative Animodel
Migration of neural crest cells is one of the critical processes of human fetal development. Malformations arise if neural crest cell migration and differentiation are impaired genetically or by toxicants. Therefore, neural crest cell migration assays are essential to evaluating potential drug toxicity for embryonic development. Our company has cranial crest cells, hindbrain crest cells, vagal crest cells, and trunk crest cells derived from mouse and human resource. The following experimental methods and systems of neural crest cell migration assays are available at Creative Animodel. Besides, designs and procedures can be adjusted for your specific needs.Vivid stainingRadioisotopic labelingTransplantation / chimerasHigh-throughput systemMigration assays through somites
Creative Animodel, as a leading contract research organization, is dedicated to providing high-quality services for drug screening and evaluation. We hold a team of toxicologists and pharmacologists with rich expertise to ensure accurate experimental designs. Our services have rapid turnarounds with cost-effective manners. If you have any needs, please feel free to contact us.
Cytotoxic T Lymphocyte Assays
Cell-mediated immunity (CMI) represents a major component of the host response against both tumor cells and intracellular pathogens. There is now plenty of evidence that cytotoxic lymphocytes can be key effector cells involved in the immune-mediated destruction of virally–infected and cancer cells. Therefore, the cytotoxic T lymphocyte (CTL) assays are most commonly used to measure CMI and assess the efficacy of cancer immunotherapy.
CTLs use two different pathways to kill virally infected cells, allografts or tumors cells. One process involves the exocytosis of granules into the cellular synaptic space (Figure 1). The granules contain various granzymes and perforin that compromise the integrity of target cell membranes resulting in necrosis. Many components of granules are important in affording protection. For instance, to protect against influenza virus infection in the lung, granzyme A, B and K are all necessary. The second process involves the induction of apoptosis in target cells through the cell surface expression of Fas-ligand on CTLs. Some viral infection studies have suggested that the level of infection may influence the balance of the two CTL killing mechanisms.
CTL Assays at Creative Animodel
The CTL assays have been used extensively in immunotoxicology research and immunotoxicity testing evaluation. We can provide a variety CTL assays for studies of immunotoxicity.51Chromium (51Cr) release assays
The most popular assay to date for evaluating cell-mediated cytotoxicity is the 51Cr-release assay. The assay is based on the passive internalization and binding of the soluble 51Cr from sodium chromate by target cells in single cell suspensions. Lysis of the target cells by added effector cells results in the release of the radioactive probe into the cell culture supernatant, which can be detected by a gamma counter.ELISPOT assays
ELISPOT assays can monitor both CTL frequency and function, such as the IFN-enzyme-linked immunospot assay. They are usually used in basic research and for monitoring cancer clinical trials. The ELISPOT assays enumerate antigen-specific lymphocyte frequency by measuring secretion of specific proteins which are the critical components of the specific pathways utilized to mediate lysis of target cells.
In Vivo Efficacy Testing
At Creative Animodel, we offer a wide range of CDX or PDX models for efficacy studies, either as subcutaneous models or as orthotopic and metastasis models in immunodeficient mice. Our tumor-bearing, humanized-xenograft models also have the potential to meet your requirement of preclinical evaluation of immunotherapies. Besides, our efficacy testing platform provides customers with study designs, which are individually tailored to your needs within a reasonable timeframe, indicating a proof of concept or therapeutic efficacy validation.
Efficacy Testing for Subcutaneous Models
• Usually 5-10 mice per group.
• Tumor grown in nude mice or other mouse strains.
• Grafting conditions: matrigel.
• Tumors are generally inoculated on the flank.
• Tumor measurement is conducted bi-weekly.
• Mono- and combination therapy is supported.
• Maximum Tolerated Dose analysis (MTD).
• In vivo Apoptosis.
• Pathway Interrogation.
• Tumor antigen testing.
• Detecting parameters contain body weight, tumor volume, serum, tumor tissue analysis etc.
Efficacy Testing on Orthotopic, Metastatic and Disseminated Tumor Models
• Usually 5-10 mice per group.
• Grafting conditions: whole body irradiation.
• Orthotopic models are established by orthotopically inoculated into colon, breast, liver, prostate, pancreas or renal. Metastatic models and disseminated models are established via intravenous injection.
• Tumor progression is monitored by in vivo bioluminescence imaging.
• Detecting parameters contain body weight, tumor burden, survival curve, hemanalysis, tissue analysis, genotyping etc.
• In vivo Apoptosis.
• Pathway Interrogation.
• Tumor antigen testing.
• Flow cytometry analysis of tumor infiltration into spleen, bone marrow, lymph nodes etc.
Assessment of Therapeutic Antibodies
The monoclonal antibody is a promising therapy at present, especially for hematological malignances such as the application of Rituximab in the treatment of NHL. Creative Animodel has established unique models and experimental techniques, enabling the translation of your developed monoclonal antibody into preclinical tests. The detection of pharmacokinetics (ELISA), bioavailability (biodistribution of radiolabeled Abs by whole-body autoradiography, organ radioactivity analysis or PET imaging), as well as the albumin-conjugate in vivo of the mAb can be achieved through our humanized-xenografts. In addition, Creative Animodel also supports combinational therapy tests to evaluate curative effect by changing administration sequences and dosages.
Customers’ benefits include the following aspects, but are not limited to:
• Accelerated drug development process.
• Rigorous and efficient work with accurate time-frame.
• Better advice on scientific issues by specialized researchers.
• High quality and reproducible experiment results.
• Professional and high-end data presentation.
Juvenile toxicology assessment is required for all pharmaceutics that is intended for potential use in children. The studies are complicated both conceptually and logistically which should take the development of the organ systems of the child into consideration. In support of a clinical trial in the pediatric population, a juvenile animal toxicity study is likely required. Development in young animals is a continuous process with different organs maturing at different rates and time. Structural and functional maturational differences have been shown to affect drug safety. Creative Animodel offers a wide range of in vivo toxicology assays including juvenile toxicology studies for you to obtain critical information on the potential safety concerns of your pharmaceutical and biopharmaceutical compounds.
Juvenile Toxicology Services at Creative Animodel
We have extensive knowledge and expertise in this area, our experienced team will design, perform, interpret and report your juvenile toxicity studies that will meet your specific objectives. The testing strategies/packages are designed based on the physical and chemical properties, the compound-type and targeted development stage(s) of your interesting compounds. In addition, we are familiar with international guidelines and can ensure the studies are designed according to the regulations of the international agencies.
Our studies include but are not limited to:Juvenile toxicity studies design——general toxicityDevelopmental toxicity studies for vaccines in rodents or rabbitsJuvenile toxicology studies in non-human primates
Typically toxicity studies are performed on the Sprague Dawley rats, however, our experts can also adapt the testing on mice, dogs, minipigs, rabbits, or cynomolgus monkeys. Different dose levels are selected according to the regulatory requirements. Other factors such as the proposed pediatric indication, the age of the intended population, the extent and timing of drug exposure, the likely target organ(s) for toxicity are also considered during the study design.
Routes of administration:Oral: gavage, dietary admixture, drinking waterDermal applicationSubcutaneous, intra-dermal, intramuscular and intraperitonealIntravenous: bolus, slow injection, continuous and intermittent intravenous infusion
Support services:Toxicokinetics, bioanalysis and clinical pathologyDevelopmental immunotoxicologyDevelopmental neurotoxicity (functional observational battery, cognitive function, neuro-histomorphometry)Genomics using the Affymetrix platformSkeletal development evaluated in vivo by X-ray, DXA, pQCT and microCT
An experienced team with state-of-the-art technologies to help you assess the toxicity riskPersonalized program design to meet your specific needs including non-standard and customized studiesServices follow regulatory guidelines to ensure test reliability, high quality, timeliness, and cost-effectivenessComprehensive supportive services
At Creative Animodel, we have well-trained and experienced experts as well as the delicate techniques that can meet the specific requirements of our clients. We can provide a fast, reliable and cost effective service to help you to evaluate the effects of your substance on the growth and development of pulmonary, immature nervous, renal, skeletal, immune and reproductive systems. If you are looking for companies that can help you with the juvenile toxicity, Creative Animodel could be your best choice, we will partner with you to design the most appropriate, cost-effective and socially responsible protocols to get the safety assurance you need. Please feel free to contact us anytime you want.
Respiratory system consists of the nasal passages, pharynx, trachea, bronchi, and lungs. Respiratory toxicity is adverse effects of respiratory system caused by exposure to chemical substances or biological products. Respiratory toxicity can induce a variety of acute or chronic morbid conditions, including local irritation, bronchitis, pulmonary edema, emphysema, pulmonary fibrosis, and cancer. Acute exposure to respiratory toxins can cause effects ranging from mild irritation to asphyxia death. Prolonged exposure to respiratory toxins can cause structural damage to the lungs, leading to chronic diseases.
Inhalation is the primary method of delivering medications to patients with respiratory diseases and is also the primary route of accidental exposure during the manufacturing, handling, or use of chemicals. Many inhaled toxins bypass the defense mechanisms of respiratory system or are activated by metabolic enzymes, resulting in respiratory toxicity and damage. Proper identification and safety assessments of potential respiratory toxins are important to chemical and pharmaceutical industries.
Respiratory Toxicology Services at Creative Animodel
The laboratory of respiratory toxicology at Creative Animodel is supported by state-of-the-art equipment and technology. Studies range from acute to chronic exposure of respiratory toxins. We maintain separate husbandry and dosing rooms in our inhalation rooms, so that dosing for animals can be achieved using either whole-body exposure or nose-only exposure system. In addition, we also provide intranasal administration and direct pulmonary administration for all species. With years of experience, we have performed in vivo respiratory toxicity testing for a range of drug candidates such as bronchodilators, anti-asthmatics, steroids, and surfactants. In general, we provide rodents and non-rodents to meet your different needs.
Our services include but are not limited to:Inhalation testing, Radiolabeled aerosol disposition studies, Bronchoalveolar lavage, Pulmonary angiography, Respiratory inductive plethysmography, and Histology assessment.
Creative Animodel provides comprehensive in vivo toxicology services with well-equipped technology platforms and experienced experts. Our services are performed in a high-efficiency and cost-effective manner. If you have any specific needs, please feel free to contact us. We are looking forward to helping you with drug screening and evaluation.
Subchronic neurotoxicity studies are carried out to determine the short-term risk of exposure to neurotoxic chemicals. At least three doses are used in these studies, including a dose that causes severe neurotoxicity, a no-observed-effect dose, and one or more intermediate dose. Animals are observed daily and weighed regularly. Besides observations of behavior and appearance as well as histopathological observations involved in acute neurotoxicity studies, subchronic studies require more detailed pathological studies as well as weekly clinical examinations.
Subchronic Neurotoxicity Studies at Creative Animodel
Four dominating neurotoxicity tests are required in subchronic neurotoxicity studies, including functional observational battery (FOB), motor activity, neuropathological evaluations, and schedule-controlled operant behavior (SCOB). We have strong expertise in the four tests to provide an elaborate subchronic neurotoxicity study.
Rats are commonly used to study subchronic neurotoxicity, such as Sprague-Dawley rats and Wistar rats. Multispecies tests are also available. Our experienced experts can design dose regimen, as well as duration and route of exposure based on your chemicals. We deliver reliable and reproducible tests and parameters required by U.S. EPA neurotoxicity guidelines.
The ReadoutsNeurobehavior: FOB, motor activity, rotarod forced activity, water maze learning and memory testing, and auditory startle habituation.Neurochemistry: neurotransmitters (such as ChE, AChE, NTE) activity assays in red blood cell, plasma, and brain samples.Neuropathology: In situ perfusion, stereology, morphometry, and qualitative neuropathological evaluations.
Creative Animodel provides both acute and subchronic neurotoxicity assays for pharmaceutical industries to supplement in vitro neurotoxicity studies. Our comprehensive and qualified neurotoxicity service package helps you fully understand the neurotoxicity of your compounds before human testing. If you are interested in our services, please do not hesitate to contact us.
The gastrointestinal (GI) tract has a unique feature of the large surface area (circa 400 m2), so it plays an important role in digestion and can receive high local or direct exposure to orally administered xenobiotics, vehicle, diet contaminants as well as dietary nutrients. Adverse drug reactions (ADR) involving the GI tract are significant and frequent problems, creating a major burden to patients, healthcare providers, and the pharmaceutical industry. The GI tract is an important target organ for toxicity in pre-clinical studies. The cells lining the crypts of the small intestine are proliferating rapidly in the body and therefore are sensitive to the effects of many therapeutic agents. The damage to stem cells within the intestinal crypts leads to the loss of cell and villus, the ulceration and inflammation of the epithelium, and the impairment of the GI tract integrity. In addition, an important consideration in the development of new drugs is the potential for off-target effects on the GI tract. A range of experimental animal models has been set up to detect possible deleterious effects to the GI tract and the potential risk in humans. It is reported that pre-clinical animal models were predictive of human GI adverse events in over 80% of cases.
Gastrointestinal Toxicology Services at Creative Animodel
While many assessments of the GI tract are often limited to measurements of transit time and observations of vomiting or diarrhea, Creative Animodel can develop methods and techniques which enable to assess specific changes in GI function at the membrane, cell, and whole animal levels. Our models can be used to understand the potential to cause GI toxicity and define the mechanism of action. Based on these results, it may be possible to determine a dosing regimen with an improved GI safety profile.
Testing compounds are administered, signs of intestinal toxicity are monitored, and suitable analysis can be performed to determine the target cell population, mechanism of action and PK/PD response. There are some assessing readouts:Physiological readouts: weight loss, diarrhoea, mucosal bleeding/occult blood, and bowel weight to length rationHistological readouts: length and number of the crypt and villus, muscle thickness, mucositis severity/ulcer size, as well as apoptosis, differentiation, and proliferation Others: protein expression and gene expression
With years of experience, Creative Animodel offers a wide range of toxicology and safety pharmacology assays. Our gastrointestinal toxicology services provide clients with high-quality toxicity data to support drug discovery and development in a cost-effective and time-saving manner. If you have any questions or specific needs, please feel free to contact us.
Inhalation toxicology is defined as the adverse effects occurring after inhalational administration. Inhalation toxicology studies can provide important information for the risk assessment of inhaled materials. Because of the large surface of lung and the close proximity of the alveolar and vascular systems, which maximizes the potential for drug delivery to the lung or systemic
circulation, drug delivery by inhalation has a proven track record for safe and effective treatment of human respiratory diseases, principally asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis and infection. However, in comparison with small molecule drug development, there exist some challenges to the development of effective and safe inhaled biological agent. Although many toxicological considerations for inhaled biopharmaceuticals are the same as small molecules, inhaled biopharmaceuticals have some specific features, such as relevant pharmacology, consistency of manufacturing processes, and immunogenicity, influence study design considerations.
Inhalation Toxicology Services at Creative Animodel
Creative Animodel provides integrated services at the early development of your inhalation drug, including providing technical and regulatory advice, conducting preliminary studies, and performing pivotal inhalation studies. We offer the following inhalation toxicology services for the development of your candidate drug:Neonatal inhalationAnti-asthmatic inhalationImmunologic sensitization via inhalationIntranasal inhalationIntratracheal inhalationAnti-asthmatic efficacyAcute to chronic toxicity, plus carcinogenicityNose-only and whole-body exposure of rodentsToxicokinetics of inhaled particlesLung function measurementRadiolabeled aerosol studies
Our AdvantagesRich experience in delivery of aerosols, vapors, and gases through the use of various nebulizers, atomizers, dry powder generators, gas/vapor generators, pressurized metered dose inhalers (MDIs), or dry powder inhalers (DPIs).A wide range of species available, including rat, mouse, dog, rabbit, guinea pig, hamster, minipig, pygmy goat, and cow.Various routes of administration, including nose only or whole body inhalation exposure (rodents), oronasal inhalation exposure (large animals), nasal dosing and intratracheal administration.Extensive knowledge and experience in aerosol science and inhalation exposure.Experience with complex test samples: powders, fibers, nanoparticles, and nanofibers.Personalized program design to meet your specific needs including non-standard and customized studies.
At Creative Animodel, we can conduct inhalation toxicity studies in accordance with international guidelines for regulatory agencies such as FDA, EPA, OECD, and others. By right of rich experience on inhalation studies, our team can provide comprehensive services of inhalation toxicology and custom solutions for global clients to meet specific requirements. If you have any questions, please feel free to contact us.
Phototoxicity is also called photoirritation. It is a kind of skin irritation induced by chemicals which requires light, but the process does not involve the immune system.
Normally percutaneous drugs and some drugs that will need systemic circulation through ingestion or parenteral administration to reach the skin and make the drugs work, all involve the potential stimulation of the skin. The drug or chemical may be stable under no illumination. Once it absorbs light, the absorbed energy produces molecular changes that will cause toxicity. The skin response resembles an exaggerated sunburn, characterized by redness and itching, pain and even fester.
Due to phototoxicity is more common and serious than photoallergy, FDA Guidance demands that any compounds or cosmetics which can absorb UVB, UVA or visible light in the range of 290-700 nm and can reach the skin or eyes need to be tested for potential phototoxicity.
Phototoxicity Testing at Creative Animodel
Since both topically applied and systemically administered drugs have the potential to induce photosensitivity, different test systems have been developed. Among that neutral red phototoxicity test is the most common method. An in vitro test determines the novel drug or compounds whether have the cytotoxic and phototoxicity effect on murine fibroblasts (3T3) in the presence or absence of UVA light.
In addition to cell test, we also prepare the animal test to meet your special needs. Including but not limited to:
Qualitative and quantitative phototoxicology in mice, rats and guinea pigsAssessment of potential damage to visceral organOcular phototoxicity in rats and rabbitsSafety assessment of photodynamic drugsSafety assessment of unique light sources
Creative Animodel has received great reputation worldwide for our high-quality services, which will support your research via improving the efficiency, saving time and expense, also decreasing the incidence of mistake. Our perfect technology platforms and expertized technicians both guarantee the result's reliability and veracity. If you have any questions, please do not hesitate to contact us. Looking forward to cooperating with you.
The major function of the immune system is to provide host integrity and to ensure appropriate function of organs and tissues. To accomplish this, it must be able to distinguish self from non-self and be able to assess tissue-specific cell status and function. As a fully dispersed system, it is represented in most tissues, organs and peripheral sites (e.g. respiratory, dermal, gastrointestinal, neurological, cardiovascular, reproductive, hepatic and endocrine). That's to say, the immune system presents a readily accessible toxicological target regardless of the route of hazardous substance exposure.
Therefore, from a risk assessment perspective, the issue is not related to whether immune exposure occurs following a hazardous substance exposure, but related to whether a given exposure is likely to produce an adverse immunotoxic outcome among susceptible populations, such as an altered immune function that may increase incidence or severity of infectious diseases or cancer.
Immunotoxicity Researches at Creative Animodel
Creative Animodel has years of experience in immunotoxicity, the research services involve:
Indicators Detected at Creative Animodel
Complete blood count and differential white blood cell countLymphoid organ weights, body weight and temperatureHistopathology, gross and microscopic examination of spleen, thymus, lymph nodes, Peyer’s patches and bone marrow
Total serum protein, albumin, globulin ratioImmunoglobulin isotype distribution of IgM, IgG, IgA and IgETotal haemolytic complement activitySerum auto-antibody screen and deposition of immunoglobulins
Immuno-staining and flow-cytometric quantitation of spleen and lymph nodes for B cells and CD4+/CD8+ T cellsMitogen stimulation assays for B and T cells (spleen)Quantitation of resident peritoneal cells and phagocytic ability
Creative Animodel has earned a great reputation worldwide with our genius services. Our high-quality services are supportive for your research, including improving the efficiency, saving time and expense, also decreasing the incidence of mistake. As a good assistant for you to discover and develop the new drug, we are looking forward to working with you side by side.
Chromosomal aberrations are the causes of numerous human genetic diseases. And there are substantial evidences that chromosomal damages and alterations in oncogenes and tumor suppressor genes of somatic cells are involved in cancer induction in humans and experimental animals. In vitro chromosome aberration test (CAT) has come to play a central role in testing mutagenic/carcinogenic potential of chemicals in most countries.
Chromosome aberration refers to the changes in the number and/or structure of the chromosomes in a biologic cell. The purpose of in vitro CAT is to identify agents which cause structural chromosomal aberrations in cultured mammalian cells. With the majority of chemical mutagens, induced aberrations are of the chromatid type, but chromosome type aberrations also occur. For most tests, therefore, it is adequate to classify aberrations into four main categories: chromosome breaks, chromosome exchanges, chromatid breaks and chromatid exchanges.
An increase in polyploidy may indicate that a chemical has the potential to induce numerical aberrations. However, this test is not designed to detect agents that cause numerical chromosomal aberrations. Therefore, a lack of polyploidy should not be considered adequate evidence that the test material does not have the potential to induce numerical aberrations, including aneuploidy.
Chromosome Aberration Test at Creative Animodel
Our in vitro chromosome aberration test can employ cultures of established cell lines, cell strains or primary cell cultures, including human cells (e.g., Chinese hamster fibroblasts, human or other mammalian peripheral blood lymphocytes). Cell cultures are exposed to the test substance both with and without metabolic activation during about 1.5 normal cell cycle lengths. At least three analyzable concentrations of the test substance can be used. At predetermined intervals after exposure of cell cultures to the test substance, the cells are treated with a metaphase-arresting substance, harvested and stained. Metaphase cells are analyzed microscopically for the presence of chromosome aberrations.
Our results of test report include but are not limited to:Signs of toxicity (e.g., degree of confluency, cell cycle data, cell counts, mitotic index);Signs of precipitation;Definition for aberrations, including gaps;Changes in ploidy;Dose-response relationship;Statistical analyses;Concurrent negative (solvent/vehicle) and positive control data.
Creative Animodel has been long devoted to helping clients to develop custom testing strategies and conduct appropriate assays to meet the unique requirements of their test compounds. Our ongoing involvement with regulatory working groups and international societies ensures that our clients have access to the latest developments in science and its applications in the regulatory environment. Our services are performed in a high-efficient and cost-effective manner. If you have any specific needs, please feel free to contact us.
Cytokines/chemokines play a crucial role in many manifestations of chemically induced immunotoxicity, including immunosuppression and immunoenhancement. Cytokines are small molecular weight proteins or peptides secreted by many cell types (particularly immune systems cells) that regulate the duration and intensity of the immune response. Type 1 cytokines (e.g., IFN-γ and IL-12) mediate the removal of malignant cells and virally infected cells, whereas Type 2 cytokines (e.g., IL-4, IL-5, IL-13) mediate the removal of soluble bacterial antigens.
Cytokine/Chemokine Assays at Creative Animodel
Effects on cytokines/chemokines can be analyzed on two different levels: mRNA and protein. The detection and quantitation of mRNA measures the presence of cytokines at a specific point in time within cells or a specific tissue, whereas protein is measured in a body fluid, possibly as a spill-over from the tissue, or in a supernatant following cell culture. The choice essentially depends on the aim of the study and on the equipment available.
Cytokine/chemokine bioactivity assays include:Cell proliferation & anti-proliferation;Cytokine secretion;Chemotaxis and enzyme induction.And key features of the assays include but are not limited to:Broad menu of over 700 targets;Validated for typical sample types (e.g., serum, plasma, supernatant, lysates);Optimized for sensitive, accurate, and consistent performance.
Creative Animodel’s immunology groups can evaluate a compound’s potential to be an immunostimulator or immunosuppressor. We can provide you with fully integrated services to support toxicology and preclinical studies that determine the safety of compounds, and define immunological endpoints and alterations of cellular function induced by test compounds. If you have any needs, please feel free to contact us.
Natural Killer Cell Assays
Natural killer (NK) cells are involved in defense against viruses and a number of tumors. NK cells kill target cells by the directed release of cytolytic granules which contain perforin, granzymes and granulysin. It plays an increasingly important role in evaluating NK cell function in immunotoxicity testing.
NK cells represent the first line to defend against transformed or virally infected cells. Upon triggering of activating receptors, NK cells can respond by secreting cytokines such as interferon-γ or tumor necrosis factor-α and by the release of cytotoxic granules, resulting in the lysis of susceptible target cells. The importance of NK cells becomes clear in patients with impaired NK cell function or development. These patients suffer from recurrent illness and have special problems in controlling viral infections despite their functional adaptive immune response. Therefore, a detailed analysis of NK cell function is of great importance.
NK Cell Assays at Creative Animodel
NK cell function can be evaluated by determining cytolytic activity against target tumor cells through the chromium 51 (51Cr)-release assay in mice and in humans, and also by determining the number of NK cells through flow cytometry. Recently, it was found that the intracellular levels of perforin, granzymes and granulysin show good correlations with NK activity in humans. And determining the intracellular levels of perforin, granzymes and granulysin by flow cytometry is also useful for evaluating the effect of chemicals on human NK cell function.
51Cr-release assays are used for the precise and accurate quantification of cytotoxicity, particularly in the study of tumor and viral cytolysis. In the assays, the target cells are radioactively labeled and then mixed with effector cells. The release of the radioactive isotope, which correlates with NK cell-mediated cytolysis, is then measured at a given time point (less than 4 hours).Flow cytometry methodologies
The flow cytometry methodologies include: 1) the measurement of NK binding to targets; 2) the measurement of NK cytotoxicity by propidium iodide staining of dead targets; 3) the contemporary measurement of binding and cytotoxicity, which gives the percentage of target cells effectively killed by the NK cells bound on their surface; 4) the measurement of intracellular levels of perforin, granzymes and granulysin in NK cells.
The development and manufacture of therapeutic antibodies, including Fc (crystallizable fragment) fusion proteins, represent a significant segment of the biopharmaceutical industry and have resulted in substantial benefits to public health. Therapeutic antibodies rely on two types of functionalities to achieve clinical efficacy: target-specific binding by the Fab (antigen-binding fragment) domain and immune-mediated effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) via interaction of the Fc domain with receptors on various cell types.
CDC: In this mechanism, the antibody binds to a target cell with high specificity through its complementary determining regions (CDR), and recruits the C1q component of the complement cascade through binding to the Fc region. The final result of the cascade is the formation of the membrane attack complex, which disrupts the target cell’s membrane and eventually leads it to lysis.
ADCC: In this mechanism, the antibody Fab binds to a target cell, and then binds to Fcγ receptors on the surface of natural killer (NK) cells (FcγRIII) and neutrophils (FcγII-A) through the Fc. Through this antibody-mediated interaction, the effector cells release cytokines and cytotoxic granules, which attack the target cell and take it towards apoptosis.
ADCC & CDC Assays at Creative Animodel
Creative Animodel possesses a customized ADCC & CDC assay platform that facilitates the selection of antibody drug candidates. Our ADCC & CDC assay services can determine the activity of the antibody and/or complement against specified target cell lines. The assays are not only as the potency assays for large release and stability testing for antibody therapeutics, but also as the key assays for the characterization and process development of therapeutic molecules. The ADCC assays can be conducted in both a primary system using human peripheral blood mononuclear cells (PBMCs), and a cell-based system using engineered NK cell lines. The readout is endpoint-driven (target cell lysis). And the CDC assays use normal human serums as the source of complement.
Key features of the assays include but are not limited to:Data readout is driven by the target cell lysis endpoint;Large panel of free target tumor cell lines are used; ADCC assay format is for at least 4 targets: HER2/ErbB2, CD20, EGFR and TNF-α;CDC assay can help predict the potential magnitude of complement-mediated target lysis;CDC assay format is for at least 2 targets CD20 and TNF-α;Personalized experimental design ensures to generate the most relevant CDC inhibition data (IC50s) with your molecules.
Whole Blood Binding Assay
Creative Animodel offers whole blood binding assay to help our clients to identify if differential binding to a specific component in the blood occurs, and interpret pharmacokinetic data. Our assays can also be used to investigate non-linear pharmacokinetics via saturation of blood binding.
Why Whole Blood Binding?
Blood is the real fluid in which drugs are transported so it is significant to address the concept of “free concentration in blood”: clearly, this is the concentration of compound not bound to plasma protein or to blood cell. Circulating free drug is in equilibrium with plasma proteins and with blood cells in the vessels. The in vitro test in plasma reduces this 3-component equilibrium to a 2-component one. If there are non-linear processes, the equilibrium among free concentrations, bound concentrations in blood cells and bound concentrations in plasma may change in a way which would not be predictable from in vitro experiments in plasma only. So the results of in vitro test in plasma may be misleading.
It must be noted that all blood cells, not just erythrocytes, can bind drugs. Using whole blood to address both partitioning and protein binding processes can provide a more realistic picture of what happens in vivo.
Our experienced experts propose that clinical ex vivo protein-binding studies should be performed on highly bound compounds (a definition of highly bound is suggested as > 95%). And if the compound is highly bound to protein or blood cell is non-linear in the tested interval, the experiment would be more appropriately performed in whole blood than in plasma.
Our Whole Blood Binding Assay
Our whole blood binding assay is performed using an equilibrium dialysis method and delivers a fraction of compound unbound to blood (fu). Blood binding is determined by using a disposable RED plate preloaded with 48 disposable tube insert. Each insert is comprised of two side-by-side chambers separated by an O-ring-sealed vertical cylinder of dialysis membrane. Dialysis is performed against isotonic phosphate buffer saline (PBS) at pH 7.4. The test-compound presenting in each compartment is quantified by HPLC-MS/MS. In our assays, you can notice neither clotting, significant hemolysis or unacceptable pH variations, nor instability at 37℃.
• High-throughput compound profiling
• Meet the customers’ special requirements
• Competitive price and fast turnaround time
Creative Animodel leverages our extensive expertise and integrated techniques to provide whole blood binding assays. With years of experience, our whole blood binding assays can provide results which are more relevant to the in vivo situation. If you have any additional requirements or questions, please do not hesitate to contact us.
Blood Partitioning Assay
Creative Animodel provides sets of ADME analysis for our global clients, including metabolism, permeability, metabolic stability and protein binding. In the aspect of protein binding, blood partitioning assay is offered to meet your project needs, which helps investigate the new drugs’ distribution between red blood cells and plasma. Blood sample extracted from diverse species, high technology platforms we provide and in-house expertized scientists all will ensure your items to proceed smoothly.
The Significance of Blood Partitioning
Blood partitioning is the ratio between red blood cells and plasma, which reflects the distribution of drugs in the blood.
• An interesting pharmacokinetic attribute of certain drugs is their extensive binding to red blood cells, which typically results in blood to plasma partitioning ratios >1. The phenomenon of preferential distribution into red blood cells is due to their affinity for carbonic anhydrase (CA) isozymes, which are present within the erythrocyte and may act as a site for sequestration of drugs. For this condition, using plasma data for pharmacokinetics prediction may be misleading.
• Due to concentrations of a drug differ between plasma and red blood cells, blood partitioning distribution of compounds is essential for analysis of the concentrations of compound in circulation. The knowledge of such partitioning can help to understand the compound’s pharmacokinetic behavior.
• Compared to plasma, drugs combining with erythrocytes may have more significant effects on compounds distribution. The blood partitioning determines the accumulation of compound in red blood cells which may reduce the available amount of compound and cause the decline of pharmacological effect.
• Incubation of Drugs in Whole Blood and Control Plasma
The test drug is spiked in fresh whole blood and control plasma. Routinely after incubation at 37 °C for 1 hour, all samples are centrifuged. Then all samples are treated with ice-cold acetonitrile containing internal standards and analyzed by LC-MS/MS.
ADME/DMPK Studies Services
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