CORE--FORMULATIONS

核心--配方

• 批准号: 6955872
• 负责人: Lisa Cencia Rohan
• 金额: $ 19.85万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6955872
• 关键词: antiAIDS agent; antibiotics; biomedical facility; biotherapeutic agent; defensins; dosage forms; local antiinfective agents; topical drug application

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.

配方核心的总体目标是为本次拨款申请的项目 1、2、3 和 4 提供预配方和配方开发支持。具体来说，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 中开发的逆环素杀微生物剂和后续类似物的预制剂化学和物理评估， 3) 开发、优化和评估项目 1 中开发的分泌 CVN 的 LAB 和项目 2 中开发的逆环素类似物的配制阴道产品 4) 对潜在的稳定性进行评估 杀菌剂候选制剂。 5) 协调项目 1、2、3 和 4 中使用的肽的合成和分配。 6) 为项目 3 提供配制产品，用于外植体模型中的评估， 7) 协助优化项目 3 中评估的外植体模型，以便与粘性产品一起使用，以及 8) 提供足够数量的配制测试杀菌剂产品，用于项目 4 中的动物安全测试。将为项目中确定的每种主要逆环素类似物开发定量方法 2. 候选杀菌剂的制剂前评估将包括药物在固体和溶液状态下的物理和化学特性。此外，将评估该核心中每个候选药物的潜在降解模式，并与项目 3 合作在体外评估急性毒性。 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估。将评估候选制剂的稳定性、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）。制剂核心还将负责协调逆环素的合成和分配。收到合成类似物后，核心将在将肽分配给项目之前进行质量控制评估和定量。该核心将直接支持项目 1、2、3 和 4。