The function of Core B: Preclinical Evaluation is to provide support for Projects 1 to 6. To accomplish this, the teams from ImQuest and Magee-Womens Research Institute (MWRI)/University of Pittsburgh will work together to (1) preclinically evaluate the dual compartment formulations from Project 1;(2) harmonize the MTSA determination of the drug candidates with tissue dosing from Project 2;(3) perform analytical and bioanalytical evaluations to quantify API concentrations in monkey tissue and fluids;(4) cross validate the ex vivo biopsy challenge with Project 4;and (5) analyze mucosal secretions from Project 4 for alterations of immune mediators. The work from this Core will confirm the safety and potency of the dual compartment formulations for licensure and further validate the use of ex vivo biopsies as surrogates for clinical efficacy. Core B will utilize cutting edge technologies that are recognized components of microbicide development algorithms to provide data required to define a rationale for continued clinical development of compounds. A primary focus will involve the efficacy of the formulated and unformulated products in cell based and explant assays. Additionally, we will utilize cell-based and explant based models to better understand the pharmacokinetics and pharmacodynamics of the microbicide products, as well as safety evaluations to confirm that the tested products cause no harm to cells, tissue, or flora of the vaginal and/or rectal compartments.
Core B will utilize cutting edge technologies that are recognized components of microbicide development algorithms to provide data required to define a rationale for continued clinical development of compounds. Assays will be performed to confirm the efficacy of test products as well as to assure that the products are safe for use as microbicide products delivered to the vagina or rectum.