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。具体地说，配方核心将1)通过协助优化实验室分泌CVN的冷冻干燥来支持项目1)提供在项目2中开发的逆转录周期素杀微生物剂和后续类似物的配方前的化学和物理评估，3)开发、优化和评估项目1中开发的用于实验室分泌CVN的配方阴道产品和项目2中开发的逆转录周期素类似物4)进行潜在的稳定性评估 杀微生物剂候选配方。5)协调项目1、2、3和4中使用的多肽的合成和分配。6)向项目3提供用于外植体模型评估的配方产品，7)协助优化项目3中正在评估的用于粘性产品的外植体模型，以及8)在项目4中提供足够数量的用于动物安全性测试的配方试验杀微生物剂产品。将为项目2中确定的每个先导逆转周期类似物开发定量方法。对候选杀微生物剂的配方前评估将包括药物在固体和溶液状态下的物理和化学表征。此外，还将评估该核心中每个候选的潜在降解模式，并与项目3合作进行体外急性毒性评估。 数据将被用来开发安全、有效和稳定的阴道制剂，然后在项目4的临床前动物试验中进行评估。将对配制的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和项目3合作)进行评估。核心配方还将负责协调逆转录周期素的合成和分配。一旦收到合成的类似物，在将多肽分发给项目之前，核心将进行质量控制评估和量化。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.