Core--Formulation Science

该项目的总体目标是将ReProtect的BufferGel技术与Starpharma的树突分子技术相结合，以开发具有双重作用模式的联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已建立的杀菌剂候选产品SPL7013与ReProtect的BufferGel技术相结合。子项目0002将寻求将ReProtect的BufferGel技术与第二代基于树突状聚合物的杀微生物剂相结合，该杀微生物剂相对于SPL7013具有更高的功效。子项目0003将评估子项目0001和0002开发的联合杀菌剂候选药物在I期临床试验中的安全性，并开发光学相干断层扫描技术，作为杀菌剂临床研究中的一种新的宫颈阴道成像技术。该核心将通过开发SPL7013和BufferGel（子项目0001）的原型配方，以及第二代基于树突状聚合物的杀菌剂候选药物和BufferGel（子项目0002），为这些项目和项目的总体目标做出贡献。将生产子项目0001和0002产生的选定原型，以支持初步的动物安全性和有效性研究。最终原型将被制造出来，以支持猕猴和GLP的临床前研究。还将生产临床试验材料以供应临床试验场地（子项目0003）。因此，该核心有四个具体目标：具体目标1（1年和2年）：基于BufferGel和SPL7013的组合开发最佳配方，并在确定时制定第二代树状大分子。具体目标2（1-4年）：提供特性良好的阴道凝胶配方，以支持项目资助中的动物功效和毒性研究。

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.