Sexual transmission of HIV is the most common means of acquiring the disease. Topical microbicides have been investigated to prevent transmission. This study will use a specific entry inhibitor, maraviroc, and a nucleotide reverse transcriptase inhibitor (NRTI), tenofovir, a dual combination which will provide a synergist effect that can enhance the efficacy of HIV microbicides via a mucoadhesive dual compartment bigel. Bigel formulation via hydrogel organogel linkages were developed and evaluated for their physicochemical characteristics, safety, and anti-HIV efficacy. In vitro diffusion studies were performed with Franz diffusion cells having effective diffusion surface area of 1.76cm2 and receiver chamber volume of 15mL. The bigel formulations showed a viscosity ranging from 14179 to 14560 cPs and had a good spreadability and acidic pH in the range of 4.0 ± 0.34 to 5.2 ± 0.18. The bigel formulations showed good anti-HIV activity at a concentration of 0.1 μg/mL. The in vitro release study of maraviroc from the bigel formulations showed a release rate ranging from 2.675 to 3.838 μg/cm2/min½ while the release rate for tenofovir ranged from 3.475 to 3.825 μg/cm2/min½. The bigel formulations were non-toxic to the human vagina as there was < 1 log10 change in Lactobacilli crispatus viability. This study successfully developed a dual compartment bigel containing maraviroc and tenofovir. BG C was found to be stable and safe towards vaginal and rectal epithelium, and it actively prevented HIV transmission. This bigel has the potential for long-term pre-exposure prophylaxis prevention of HIV transmission.

中文翻译：

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用于 HIV 预防的含有替诺福韦和马拉韦罗的粘膜粘附 bigel 的开发和评价

HIV 的性传播是最常见的感染途径。已经研究了局部杀微生物剂以防止传播。本研究将使用特定的进入抑制剂马拉韦罗和核苷酸逆转录酶抑制剂 (NRTI) 替诺福韦，这是一种双重组合，将提供协同效应，可通过粘膜粘附双隔室 big​​el 增强 HIV 杀菌剂的功效。开发了通过水凝胶有机凝胶连接的 Bigel 制剂，并评估了它们的物理化学特性、安全性和抗 HIV 功效。使用具有 1.76cm2 有效扩散表面积和 15mL 接收室容积的 Franz 扩散池进行体外扩散研究。bigel 配方的粘度范围为 14179 至 14560 cPs，并具有良好的铺展性和 4.0 ± 0.34 至 5.2 ± 0.18 的酸性 pH 值。bigel 制剂在 0.1 μg/mL 的浓度下显示出良好的抗 HIV 活性。bigel 制剂中马拉韦罗的体外释放研究显示释放速率范围为 2.675 至 3.838 μg/cm2/min½，而替诺福韦的释放速率范围为 3.475 至 3.825 μg/cm2/min½。bigel 制剂对人体阴道无毒，因为卷曲乳杆菌活力的变化 < 1 log10。本研究成功开发了一种含有马拉韦罗和替诺福韦的双隔室 big​​el。BG C 被发现对阴道和直肠上皮是稳定和安全的，它可以积极地阻止 HIV 传播。