Core--Formulation Science

该计划的总体目标是将联合收割机的BufferGel技术与Starpharma的树枝状聚合物技术相结合，以开发具有双重作用模式的组合局部杀微生物剂候选物，以对抗艾滋病毒的性传播。子项目0001将寻求将联合收割机Starpharma已确定的候选杀微生物剂SPL 7013与ReProtect的BufferGel技术相结合。子项目0002将寻求将联合收割机的BufferGel技术与第二代树枝状聚合物基杀微生物剂相结合，该杀微生物剂相对于SPL 7013具有更高的功效。子项目0003将评估子项目0001和0002中开发的复合杀微生物剂候选物在试验性I期临床试验中的安全性，并开发光学相干断层扫描作为杀微生物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SPL 7013和BufferGel（子项目0001）以及第二代树枝状聚合物基杀微生物剂候选物和BufferGel（子项目0002）的原型配方，为这些项目和该计划的总体目标做出贡献。将生产从子项目0001和0002中产生的选定原型，以支持初步的动物安全性和有效性研究。将制造最终原型，以支持猕猴和GLP临床前研究。还将生产临床试验材料，以供应临床试验中心（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）：基于BufferGel和SPL 7013的组合开发最佳配方，并在确定第二代树枝状聚合物时进行配方。具体目标2（1-4年）：提供良好表征的阴道凝胶制剂，以支持计划项目资助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生产的规模扩大，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生产和正式ICH稳定性研究，以支持人体临床试验。

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.