Given the significant anatomical and physiological differences in the rectal and vaginal compartments it is essential to design rectal specific microbicide products to effectively inhibit rectal transmission of HIV. The overall goal of the Product Development Core (Core B) is in the provision of formulated Griffithsin (GRFT) gel products and quality, physiochemical, safety, and efficacy assessments for these products. Specifically Core C will provide preformulation data, formulation development efforts, and formulation assessment evaluations in support of Projects 1, 2, and 3 as well as Cores C and D. Formulation strategies within the scope of Core activities will be initiated utilizing knowledge obtained from previously developed rectal and vaginal GRFT gel products. Product attributes will be modified to obtain defined target specifications suitable for rectal application. The rectal specific GRFT product will be tested for safety and efficacy using an excised mucosal tissue explant model. A final formulation will be chosen based on successful achievement of defined target product profiles. Once the newly developed rectal GRFT formulation is obtained it will be scaled up and manufactured to support GLP animal safety testing studies and other preclinical assessments planned within Projects 1 and 2. Manufacture of GMP quality material will be achieved through a contract research organization within Project 1. Core B will be responsible for methods transfer, provide assistance with development of batch records generated, assist in protocol development for product assessment methods established for GMP product release, and review stability results obtained. Additionally, Core B will design a rectal specific GRFT combination product with enhanced potency as a second generation product. Efforts toward this end will be initiated through application of a screening algorithm to identify the most effective combination. Lead secondary antiretroviral candidates include tenofovir (TFV) and dapivirine(DPV). TFV and DPV are the lead ARV candidates currently being evaluated in the clinic. Quantitative assays to support formulation efforts have been developed in the laboratory for GRFT, TFV, and Dapivirine. This Core plays a critical role in the activities described within the PREVENT Program. The products and testing parameters developed within this core will be utilized by all projects and cores within the program.
Product Development Core (Core B) will provide formulation development focused on the development of the anti-HIV protein griffithsin single entity and combination products. This Core will also conduct activities to ensure the safety of gels advancing to clinical trials.