Core--Formulation Science

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The overall goal of this program is to combine ReProtect's BufferGel technology with Starpharma's dendrimer technology in order to develop combination topical microbicide candidates with a dual mode of action against the sexually transmission of HIV. Subproject 0001 will seek to combine Starpharma's established microbicide candidate SPL7013 with ReProtect's BufferGel technology. Subproject 0002 will seek to combine ReProtect's BufferGel technology with a second generation dendrimer based microbicide microbicide with enhanced efficacy relative to SPL7013. Subproject 0003 will assess the safety of the combination microbicide candidates developed in Subprojects 0001 and 0002 in pilot Phase I clinical trials and develop optical coherence tomography as a new cervicovaginal imaging technique in microbicide clinical research. This Core will contribute to each of these projects and the overall goal of the program through the development of prototype formulations of SPL7013 and BufferGel (Subproject 0001) and second generation dendrimer based microbicide candidates and BufferGel (Subproject 0002). Selected protoptypes arising from both Subprojects 0001 and 0002 will be maunfactured to support preliminary aminal safety and efficacy studies. Final prototypes will be maunfactured to support macaque and GLP pre-clinical studies. Clinical trial material will also be maunfactured to supply the clinical trial site (Subproject 0003). As a result this Core has four Specific Aims: Specific Aim 1 (Year 1 and 2): Develop optimal formulations based on a combination of BufferGel and SPL7013, and to formulate second generation dendrimers as they are identified. Specific Aim 2 (Years 1-4): Provide well-characterized vaginal gel formulations to support animal efficacy and toxicity studies in the Program Project Grant. Specific Aim 3 (Year 1 and 3): Complete scale-up of final gel prototypes and GMP manufacturing at the CPST to support preclinical GLP Safety/Toxicity Studies. Specific Aim 4 (Year 2 and 4): Complete GMP Manufacturing and Formal ICH Stability Studies at the CPST to support human clinical trials.