INVITEK Inc. is a Preclinical CRO, located in the San Francisco Bay Area; Hayward, California, offering a wide range of Preclinical Services in-vivo and in-vitro for screening and evaluation of new drugs and formulations for early drug discovery and development.
The scientific team of Invitek consists of highly-qualified and motivated individuals with more than 20 years of combined hands-on experience in innovative drug discovery and development.
Our highly consultative method ensures that each drug-development process receives personal consideration and commitment. We provide exceptional Preclinical service to meet your unique needs.
Acute and Chronic DSS-induced colitis
Oxazolone-induced colitis in mice and rats
Acetic acid-induced colitis
Preclinical animal models of IBD plays an important role in the understanding of the pathogenesis of the disease. IBD is a chronic inflammatory disease of unknown etiology with two major categories: Ulcerative Colitis (UC) and Crohn’s Disease (CD). The main features of IBD include diarrhea, associated with blood, mucus, and pus in the stool. UC characterized by inflammation of the colon mucosa, depletion of the mucus-forming goblet cells, irregularity of the crypts, and crypt abscesses, in addition, neutrophils surrounding the local blood vessels, the lamina propria shows plasma cell infiltration and lymphoid aggregates. Whereas, in Crohn’s disease inflammatory lesions particularly found in the ileum and colon. These lesions transmural with extensive granuloma formations.Invitek offers preclinical animal models of colitis; DSS, TNBS, and oxazolone in mice and rats for the screening, testing, and evaluation of new drugs and formulations.
DSS (Dextran Sodium Sulfate) Induced Colitis:
Dextran sulfate sodium (DSS)-induced colitis model is widely used because of its simplicity and many similarities with human ulcerative colitis (UC). Acute and chronic models of intestinal inflammation achieved by modifying the concentration of DSS and the frequency of administration.
Acute colitis model induced by providing a single cycle of DSS in drinking water for five to seven days, followed by plain drinking water for another five to seven days.
Chronic colitis model induced by providing three cycles of DSS in drinking water for five days, with intervals of five to seven days of plain drinking water. In general body weight, DAI and severity scoring is performed.
Oxazolone Induced Colitis:
Oxazolone-induced colitis in mice and or rats constitutes a satisfactory animal model of UC, with a high degree of similarity to the histopathological characteristics and distribution of inflammation. First, animals pre-sensitized with oxazolone solution in ethanol for five days, and then intrarectal administration of oxazolone performed under light anesthesia.
TNBS Induced Colitis:
TNBS induced colitis is a commonly used animal model that shares many properties with human Crohn’s disease (CD). The model is highly reproducible and technically simple, therefore, used to screen potential therapeutic agents. Colitis induced by the intrarectal administration under light anesthesia.
Acetic-Acid Induced Colitis:
Colitis induced by intrarectal administration of 3.5-4% Acetic Acid in water under light anesthesia.
Preclinical animal models contribute to recent advances in the understanding of the immunopathology of Rheumatoid Arthritis (RA). Certain aspects simulate the clinical, immunological, and histopathological features of the disease. In addition animal models continue to provide the means of testing and evaluating new therapeutic agents for the treatment of rheumatoid arthritis.
Invitek offers several rodent models of Rheumatoid Arthritis and inflammation for the screening, testing and evaluating new drugs and formulations.
Collagen Induced Arthritis (CIA) Model:
Collagen Induced Arthritis (CIA) is a widely used and well characterized animal model of autoimmunity. This model is extensively studied because of its similarities to human Rheumatoid arthritis. CIA is linked to MHC-class II molecules and depends on the species of type II collagen used for immunization. Arthritis is induced in genetically susceptible strain of mice or rats by immunization with type II collagen (bovine or chicken).Immunization in mice done in Complete Freund’s Adjuvant (CFA) containing M. tuberculosis H37RA. In addition a booster injection on day 21. Symptoms begin appearing within 5-7 days after booster dose.Immunization in rats done in Incomplete Freund’s Adjuvant (IFA). In addition booster injection on day 7. Symptoms begin appearing within 3-5 days after booster dose.
Adjuvant Induced Arthritis (AIA) Model:
Adjuvant Induced Arthritis (AIA) is a T-cell mediated autoimmune arthritis, therefore frequently used to study immunological aspect of Rheumatoid arthritis (RA) and other arthritic or inflammatory disease. AIA is a well established experimental animal model and frequently used for testing and evaluating anti-inflammatory drugs.Adjuvant arthritis performed in genetically susceptible strain of rats through immunization with Incomplete Freund’s Adjuvant (IFA) containing M. butyricum. Symptoms start appearing 8-10 days after immunization and last for 15-20 days.
Antigen Induced Arthritis (AIA) Model:
Antigen Induced Arthritis (AIA) is a T-cell mediated autoimmune arthritis. The arthritis remains confined to the injected knee joints and therefore is used to study immunological aspect of Rheumatoid arthritis (RA).Arthritis induced by direct injection of methylated Bovine Serum Albumin (mBSA), an antigen, into the knee joint of pre-immunized animals. mBSA injected into the right knee joint to induce unilateral arthritis while the left knee joint injected with saline as the control.
SCW‐Induced Arthritis Model:
The Streptococcal Cell Wall (SCW) induced arthritis model closely simulates many features of Rheumatoid arthritis (RA). A single intraperitoneal injection of group-A streptococcal peptidoglycan‐polysaccharide (PG‐PS) cell wall fragments induce an initial acute inflammation phase, followed by a chronic inflammatory phase. As a result this model is frequently used for the assessment of therapeutic compounds on the acute and chronic arthritis studies
Hepatic Fibrosis/Liver Fibrosis
Hepatic fibrosis refers to liver injury, characterized due to excessive production and deposition of extracellular matrix (ECM) molecules. The advanced stage characterized by widespread fibrous scarring called cirrhosis. Experimental animal models of hepatic fibrosis provide significant tools to understand the cellular and molecular mediators of fibrosis in a various manner during both progression and recovery. Several approaches to induction of fibrosis have been developed. Among these, CCl4 and TAA intoxication in rats and mice are the most widely used method for induction of hepatic fibrosis. CCl4 and TAA models best characterized with respect to histological, biochemical, cell, and molecular changes associated with the development of fibrosis.
Invitek offers several hepatic fibrosis models in rats and mice for screening, testing, and evaluation of new drugs and formulations.
Hepatic Fibrosis Model-Induced By CCl4 In Rats and Mice
Hepatic fibrosis induced by Intraperitoneal (i.p.) injection of CCl4 in rats and mice. Following acclimation, animals assigned to different groups according to their body weight and injected CCl4 intraperitoneally (i.p.) mixed with Olive oil/corn oil/mineral oil twice or thrice weekly for 4-12 weeks. Test articles dosed via either of the routes of the administration [PO, IP, and SC] for 4-16 weeks.
Hepatic Fibrosis Model-Induced By TAA In Rats and Mice
Thioacetamide (TAA) is another well-established model of experimental liver fibrosis in rodents. Hepatic fibrosis induced by intraperitoneal (i.p.) injection of TAA or orally through drinking water in rats or mice. TAA-reversal serves as a good model to test potential antifibrotics.
Non-Alcoholic Fatty Liver Disease (NAFLD)
Non-Alcoholic fatty liver disease (NAFLD) represents a spectrum of liver disease associated with fibrosis, cirrhosis, steatohepatitis and hepatocellular carcinoma. NAFLD also associated with obesity, diabetes, and insulin resistance. Genetically and dietary manipulated animal models best-characterized the models of NAFLD.
Invitek offers both genetic and dietary manipulated mouse and rat models of NAFLD
The incidence of diabetes mellitus increasing worldwide at an alarming rate. The increase due to population growth, obesity, and sedentary lifestyle. Diabetes associated with other complications, retinopathy, nephropathy, coronary heart disease, peripheral arterial disease, and cerebral vascular diseases. In general, diabetes categorized into two types: insulin dependent Type-I and non-insulin dependent (insulin-resistant) Type-II. Type-II insulin-resistant diabetes mellitus accounts for 90-95% of all diabetes.Experimental animal models produced spontaneously by selective inbreeding and or by genetic modification plays important role in understanding the pathogenesis and its complications.Invitek offers several rodents models for screening, testing and evaluating new drugs and formulations for Type-I and Type-II diabetes mellitus.
TYPE I Diabetes
TYPE II Diabetes
Diabetic Nephropathy Models
Diabetic Wound Healing Models
Hyperinsulinemic-Euglycemic Clamp (HEGC) Study
Hyperinsulinemic-Euglycemic Clamp, or insulin clamp, is the most useful means of assessing insulin action in vivo. During an insulin clamp, hyperinsulinemia is accomplished by a constant insulin infusion. Euglycemia is maintained through concomitant glucose infusion at a variable rate. This variable glucose infusion rate (GIR) is determined by measuring blood glucose at different intervals throughout the experiment and adjusting the GIR accordingly. The GIR is indicative of whole-body insulin action, as the animal with enhanced insulin action requires a greater GIR.Insulin sensitivity calculated by GIR from the concentration of glucose solution that is infused, flow rate, the time between change of flow rates, and weight of animals.
Glucose Tolerance Test
The glucose tolerance test (GTT) used to measure individual with normal or impaired glucose tolerance with Type II diabetes. Glucose concentration and insulin levels measured at different time points after glucose administration.Invitek offers Glucose Tolerance Test in the various strain of mice and rats such as db/db, ob/ob, DIO, STZ and DIO rats and ZDF fa/fa rats through following the route of glucose administration.
Obesity is one of the most critical chronic metabolic disorders of the future in humans; it affects more than 300 million people worldwide according to WHO. The prevalence of obesity predominant in the United States and slowly gaining entry into developing countries as well. This condition results from a prolonged imbalance between the levels of energy intake and expenditure with the resultant surplus being stored as body fats. Obesity also linked with other conditions, such as hyperglycemia, hyperlipidemia, and coronary heart disease.
Experimental animal models produced spontaneously by selective inbreeding, genetic modification, and dietary modification are essential tools for understanding the pathogenesis, complications, and testing of various therapeutic agents. Invitek offers several rodent models, ob/ob, DIO and ZDF rat model for the screening and evaluating new drugs and formulations.
Ob/Ob Mouse Model
The obese spontaneous mutant model developed by the Jackson Laboratory in 1949 by a spontaneous mutation in the V stock. Mice exhibit obese, hyperphagia, a diabetes-like syndrome of hyperglycemia, glucose intolerance, and elevated plasma insulin. Homozygous gain excess weight and deposit excess fat. The obesity characterized by the increase in both the number and the size of adipocytes. Ob/ob mouse an excellent model for the evaluation of new drugs and formulations.
DIO (Diet-Induced Obesity) Mouse Or Rat Model
Obesity is a defined as a metabolic syndrome, which is characterized by the concurrent existence of dyslipidemia, hyperglycemia, hyperinsulinemia, and hypertension. C57BL/6 inbred strain provides an excellent model to study development/prevention, because of its susceptibility and related disorder that are highly analogous to those conditions related to humans. C57BL/6 mice, when mice fed on 60% Kcal high-fat diet for 4-8 weeks they develop the symptoms of metabolic syndrome.
ZDF Fa/Fa Rat Model
The Zucker Diabetic Fatty (ZDF) rat an animal model of Type II diabetes based on impaired glucose tolerance caused by the inherited insulin-resistance gene fa. The genetic defects lead to obesity, hyperphagia, hyperlipidemia, and hyperinsulinemia. Homozygous (fa/fa) Zucker diabetic fatty (ZDF) rats used as a model of Type II diabetes study, while heterozygous (fa/+) ZDF rats used as non-diabetic controls.
Xenograft tumor models:
Immunodeficiency mouse models such as nude (nu) strains and the severe combined immunodeficiency (scid) strains most commonly used for human xenograft tumor transplantation. Nudes (nu) functionally deficient of T-cell and other defects therefore, easy to measure the subcutaneous tumor growth . The SCID mice also deficient of functional T-cells and B-cells and readily accept human xenograft. Both of these disease models mimics human diseases and provides very useful information.Invitek offers in vivo xenograft tumor models in both nude (nu) and the severe immunodeficiency (scid) strains. Tumors transplanted using human carcinoma cell lines used for evaluating therapeutic properties of new drugs and formulations.
“Invitek intends to establish more cell lines of the NCI panel which are tumorigenic in mice.”
Syngenic tumor models:
Invitek also offers syngenic tumor models. Tumors developed by using tissue from the same genetic background strain of mouse and used for testing and evaluating new drugs and formulations.
Measurement Of Tumor Volume
Tumor volume (mm3) measured with calipers and calculated as (W2 x L) / 2, where W is width and L is length.
The tumor volume at day n is expressed as Relative Tumor Volume (RTV) and caculated according to the following formula: RTV = TVn/TV0, where TVn is the tumor volume at day n and TV0 is the tumor volume at day 0.
The T/C% is determined by calculating RTV as T/C% = 100 x (mean RTV of treated group)/(mean RTV of control group).
The tumor growth inhibition rate (IR) calculated using the formula IR (%) = (1 – TWt/TWc) x 100, where TWt and TWc are the mean tumor weight of treated and control groups, respectively.
Multiple Sclerosis (MS) is an autoimmune condition in which the immune system attacks the central nervous system (CNS), leading to demyelination of focal areas and inflammation. Most common debilitating neurological diseases in young adults. The pathogenesis of the disease unclear and etiology seems to dependent on genetic and environmental factors.Experimental Allergic Encephalitis (EAE) is a well-established animal model of MS, resembles specific features similar to histopathology and neurobiology in humans. EAE induced in laboratory animals to investigate therapeutic properties of new drugs and formulations. EAE models help in understanding the mechanisms of T-cell-mediated immune damage of the CNS, and the associated factors to the cascade of innate immunity. EAE induced in a number of different animal species but, mice and rats are the most commonly used species. Invitek offers following EAE models in Rodents
MBP (Myelin Basic Protein) Induced EAE In Rats
The Lewis rats immunized with Myelin basic protein (MBP) in Freund’s adjuvant, injected subcutaneously into the subplantar region of the hind paw. Clinical symptoms start developing around day 10 with the loss of tail tone “limp tail” and hind legs paralysis by day 14. The peak period is around day 14/15 and then animal starts recovering. This is an acute model of EAE.Therapeutic properties of new drugs and formulations can evaluate in this model, in a preventive as well as curative approach. Test article can dose via either of the routes of the administration [PO, IP, and SC]. Body weight loss and the clinical sign of symptoms observed on regular basis.This model is approximately 21 days long
MOG (Myelin Oligodendrocyte) Induced EAE In Mice
EAE induced in C57BL/6 mice by immunization with MOG peptide (35-55) in CFA (complete Freund’s adjuvant) with Mycobacterium tuberculosis and Pertussis toxin. Result in a paralytic condition, start with tail muscle “limp tail” and hind legs, then paraplegia with severe forelimb weakness. The symptoms start appearing 8 to 14 days after immunization and stay chronically paralyzed for the duration of the experimentTherapeutic properties of new drugs and formulations can evaluate in a preventive as well as curative approach. Test article can dose via either of the routes of the administration [PO, IP, and SC]. Body weight loss and the clinical sign observed daily. This model is approximately 35 to 36 days long
PLP (Proteolipoprotein) Induced EAE In Mice
This model resembles the remitting-relapsing form of MS. EAE induced in SJL mice by immunization with PLP peptide (139-151) in CFA (complete Freund’s adjuvant) containing Mycobacterium tuberculosis and Pertussis toxin. Result in a paralytic condition. The symptoms start appearing 11 to 14 days after immunization, and peak reaches around 20 to 21 days and then they start recovering fully or almost fully from the first wave of paralysis. After a disease free period of 10 to 14 days, the second wave of paralysis (relapse) started and peak reaches around 40 to 42 days.
Mice started treating with potential therapeutic from the day of immunization as “preventive treatment” to test the effect of the test article on the development of the first wave. Whereas, treatment can also start at the onset of the clinical sign of EAE to test the effect of the test article on the development of the second wave of paralysis. This model approximately 25 to 50 days long.
EAE –Using MSCH (Mouse Spinal Cord Homogenate) In Mice
EAE induced in SJL mice by immunization with MSCH, myelin and myelin component in CFA (complete Freund’s adjuvant) with Mycobacterium tuberculosis and Pertussis toxin. Result in a condition similar to those of MS. Start with tail muscle “limp tail” and hind legs, then paraplegia with severe forelimb weakness. Induction of EAE depends on the concentration of pertussis toxin. New drugs and formulations can evaluate in a preventive as well as curative approach. Test articles can dose either of the routes of the administration [PO, IP, and SC]. Body weight loss and the clinical sign and symptoms observed daily. This model approximately 21 days long.
Carrageenan Induced Paw Edema:
Carrageenan induced paw edema is an acute non-immune, well established and highly reproducible animal model of inflammation. The cardinal signs of inflammation include edema, hyperalgesia, and erythema, which develop immediately after the subcutaneous injection of carrageenan. Animals assigned to different groups and dosed with respective test articles. After 30 minutes of administration of test articles, carrageenan suspension injected subcutaneously in the sub-planter region of the right hind paw, while the contralateral paw (left ) serves as a control. Paw volume or paw thickness measured at different time points after the injection. Paw volume measured using plethysmometer, while paw thickness measured using a caliper. In addition level of serum cytokines and PGE2 measured by an enzyme-linked immunosorbent (ELISA) assay.
LPS Induced Inflammation:
Sepsis is a systemic response to serious infection and has a poor prognosis when associated with organ dysfunction, hypo profusion, and hypotension. Sepsis initiated by exposure to lipopolysaccharide (LPS), a gram-negative bacteria membrane. This results in the overproduction of host inflammatory cytokines, such as TNF-α, IL-1β, IL-6, IL-10 which up-regulate the expression of inducible nitric-oxide (iNOS).Following acclimatization, animals assigned to different groups and dosed with respective test articles. An hour after administration of test articles, animals injected intraperitoneally with LPS. Survival rates monitored at different time points. In addition, serum cytokines levels analyzed.
Pharmacokinetic (PK) data is a key requirement in the evaluation of new drugs and formulations. A quantitative measure of drug exposure is essential for the sound interpretation of pre-clinical efficacy studies. PK data is also requisite before toxicology studies can be performed.PK samples are collected at various time points as per protocol and analyzed for drug concentrations. The time points depending on the nature of compound and route of administration.
Pharmacokinetic Study In Disease Model
Invitek offers Pharmacokinetics in disease models for better understanding of absorption and bioavailability.
Toxicokinetics used primarily for establishing relationships between exposures in toxicology experiments in animals and corresponding exposures in humans.Plasma samples generated in toxicology studies and the resultant concentration data used for interpreting the result using the industry-standard software.
Invitek offers non-GLP toxicology studies. Non-GLP toxicity studies intended to provide a preliminary assessment of a drug’s safety. Non-GLP tox studies have the following advantage:
Invitek, Inc. has not received any reviews.
Invitek, Inc. has not received any endorsements.