CORE--FORMULATIONS

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The overall goal of the Formulations Core is to provide preformulation and formulation development support for Projects 1,2, 3, and 4 of this grant application. Specifically the Formulations Core will 1) Support Project 1 by assisting in the optimization of the lyophilization of LAB secreting CVN 2) Provide preformulation chemical and physical evaluations of retrocyclin microbicide agents and subsequent analogs developed in Project 2, 3) Develop, optimize, and assess formulated vaginal products for LAB secreting CVN developed in Project 1 and Retrocyclin analogs developed in Project 2 4) Conduct stability evaluations for potential microbicide candidate formulations. 5) Coordinate the synthesis and distribution of peptide for use in Projects 1, 2, 3, and 4. 6) Provide Project 3 with formulated products for evaluation in the explant model, 7) Assist with optimization of the explant model being evaluated in Project 3 for use with viscous products, and 8) Provide sufficient quantity of formulated test microbicide products for animal safety testing in Project 4. Quantitative methods will be developed for each lead retrocyclin analog identified in Project 2. Preformulation assessment of microbicide candidates will consist of physical and chemical characterization of the drug in both the solid and solution state. Additionally, potential modes of degradation will be evaluated for each candidate in this core and acute toxicity evaluated in vitro in collaboration with Project 3. These data will be utilized to develop safe, effective, and stable vaginal formulations which can then be evaluated in preclinical animal testing in Project 4. Formulated microbicidal candidates will be assessed for stability, rate of drug release, acute toxicity (in collaboration with Project 3) and anti-STI activity (in collaboration with Projects 2 and 3). The Formulation Core will also be responsible for coordination of retrocyclin synthesis and distribution. Upon receipt of synthesized analogs, quality control evaluations and quantitation will be conducted by the core prior to distribution of the peptide to the projects. This Core will directly support Projects 1,2,3, and 4.