工程性阴道膜平台用于粘粘和持续的药物释放,用于HIV-1预防
Jing Li1, Sravan Kumar Patel1, Yvonne Sweeney2
1Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA; Magee-Womens Research Institute, Pittsburgh, PA, USA.
概括
一种新型的长效阴道膜提供HIV-1整合酶抑制剂,有望改善对暴露前预防的坚持. 这种二氧化基和PLACL薄膜在体内维持了有效药物度两个星期,没有毒性.
科学领域:
- 生物材料科学 生物材料科学
- 制药科学 制药科学
- 预防传染病 预防传染病
背景情况:
- 用户的坚持对于局部暴露前预防 (PrEP) 对HIV-1的有效性至关重要.
- 长效PrEP配方可以潜在地克服与日常或性交依赖的治疗方案相关的坚持挑战.
研究的目的:
- 开发和描述一种长效的阴道膜,用于持续输送整合酶抑制剂MK-2048,用于预防HIV-1.
- 为了评估薄膜的粘粘度,药物释放动力学,毒性和体内疗效.
主要方法:
- 合成和描述具有不同LA:CL比率的多聚乳-co-Ɛ-caprolactone (PLACL) 共聚合物.
- 通过溶剂造制造硫化和PLACL复合薄膜.
- 在体外评估物理化学性质,MK-2048释放动力学,粘膜粘合,透性和细胞毒性.
- 在猪尾的体内评估,以确定阴道液和组织中的药物度和毒性.
主要成果:
- 薄膜配方 (化基和PLACL 80) 的弹性与市场上销售的薄膜相比,药物释放速度较慢.
- 化基的加入显著增强了粘膜粘合和药物透性.
- 试验室研究显示没有毒性和与自由MK-2048.8相比的抗HIV活性.
- 在的体内研究表明,至少两周的药物度高于IC95,没有观察到毒性.
结论:
- 开发的硫化基和PLACL阴道膜是HIV-1预防的有前途的长效药物输送平台.
- 这一策略提供了一个潜在的解决方案,以改善用户对局部PrEP的坚持.
- 进一步开发这种聚合物薄膜平台可以提高持续的药物释放和体内性能.
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