Pharmacokinetics for Experimental Rheumatoid Arthritis Treatment

Department of Veterans Affairs Network

Contracting Office (NCO) 05 Title: A Joint Targeted Drug Delivery Approach for Arthritis Therapy Toxicity and Pharmacokinetics 1. Purpose This Sources Sought Notice is issued solely for market research in accordance with FAR Part 10.

This is not a solicitation, and it does not commit the Government to issue a solicitation or make an award. The Department of Veterans Affairs (VA) seeks to identify qualified vendors capable of performing preclinical toxicology and pharmacokinetic (PK) studies on an experimental Rheumatoid Arthritis treatment involving peptide-displaying liposomes containing dexamethasone. 2. Requirement Overview The VA requires a contractor to perform GLP-compliant toxicity testing and GLP or non GLP pharmacokinetic studies in adult rats. These studies support advancement toward a future FDA Pre IND meeting for the patented joint-targeted liposomal delivery system developed under prior VA-funded research. 3. Summary of Required Services

A. Toxicity Studies (GLP Required) Receive peptide displaying liposomes containing 150 mg dexamethasone, 80% encapsulation efficiency, with Certificate of Analysis. Conduct single dose intravenous toxicity testing in 20 32 rats (male and female). Record clinical observations, weight, and food intake over a 14 day period. Conduct blood testing for organ damage markers (liver, kidney, heart, muscle, etc.). Perform euthanasia, necropsy, and histopathology of major organs.

B. Pharmacokinetic (PK) Studies (GLP or non GLP) Administer single IV doses to 12 24 rats (balanced sexes). Observe and weigh animals before and after dosing. Collect blood samples at 8 10 defined time points (10 min through 48 hours). Process plasma and store at 20°C. Perform chemical extraction and LC MS/MS quantification of dexamethasone and metabolite 6 hydroxydexamethasone (6OHDEX). Generate PK parameters (t½, Cmax, AUC, etc.).

C. Final Deliverable Comprehensive written report summarizing toxicity, PK parameters, and analytical results. 4.