Core--Formulation Science

该计划的总体目标是将ReProtect的BufferGel技术与StarPharma的树枝状大分子技术相结合，以开发具有双重作用模式的组合局部杀微生物剂候选药物，以对抗艾滋病毒的性传播。子项目0001将寻求将StarPharma已有的杀微生物剂候选SPL7013与ReProtect的BufferGel技术相结合。子项目0002将寻求将ReProtect的BufferGel技术与第二代树枝状大分子杀微生物剂相结合，相对于SPL7013具有更强的药效。子项目0003将评估子项目0001和0002中子项目0001和0002开发的候选杀微生物剂在第一阶段临床试验中的安全性，并开发光学相干断层扫描作为一种新的宫颈阴道成像技术用于杀微生物剂临床研究。该核心将通过开发SPL7013和BufferGel的原型配方(子项目0001)和第二代树枝状大分子候选杀微生物剂和BufferGel(子项目0002)，为每个项目和计划的总体目标做出贡献。从0001和0002两个子项目产生的选定原型将被制造出来，以支持初步的氨基安全性和有效性研究。最终的原型将被制作出来，以支持猕猴和GLP的临床前研究。还将制作临床试验材料，以提供临床试验场地(子项目0003)。因此，该核心有四个具体目标：具体目标1(第1年和第2年)：开发基于BufferGel和SPL7013组合的最佳配方，并在确定第二代树枝状大分子后配制它们。具体目标2(第1-4年)：提供具有良好特性的阴道凝胶制剂，以支持计划项目赠款中的动物疗效和毒性研究。 具体目标3(第1年和第3年)：在CPST完成最终凝胶原型和GMP生产的放大，以支持临床前GLP安全性/毒性研究。具体目标4(第2年和第4年)：在CPST完成GMP制造和正式的ICH稳定性研究，以支持人类临床试验。

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.