CORE--FORMULATIONS

配方核心的总体目标是为本赠款申请的项目1、2、3和4提供配方前和配方开发支持。具体而言，制剂核心将1）通过协助优化分泌CVN的LAB的冻干来支持项目1，2）提供项目2中开发的逆转录细胞周期素杀微生物剂和后续类似物的制剂前化学和物理评价，3）开发、优化、并评估在项目1中开发的分泌CVN的LAB和在项目2中开发的Retrocyclin类似物的配制阴道产品进行潜在稳定性评估 杀微生物剂候选制剂。5)协调用于项目1、2、3和4的肽的合成和分配。6)为项目3提供用于外植体模型评价的配制产品，7）协助优化项目3中评价的外植体模型，以用于粘性产品，8）为项目4中的动物安全性试验提供足量的配制试验杀微生物剂产品。将为项目2中确定的每种主要逆转录细胞周期蛋白类似物开发定量方法。候选杀微生物剂的配方前评估将包括固体和溶液状态下药物的物理和化学特性。此外，将评价该核心中每种候选物的潜在降解模式，并与项目3合作进行体外急性毒性评价。这些 数据将用于开发安全、有效和稳定的阴道制剂，然后可以在项目4的临床前动物试验中对其进行评价。将评估配制的候选杀微生物剂的稳定性、药物释放速率、急性毒性（与项目3合作）和抗性传播感染活性（与项目2和3合作）。制剂中心还将负责协调retrocyclin的合成和分布。收到合成类似物后，在将肽分配给项目之前，将由核心进行质量控制评价和定量。该核心将直接支持项目1、2、3和4。

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.