Tyo Kevin M, Vuong Hung R, Malik Danial A, Sims Lee B, Alatassi Houda, Duan Jinghua, Watson Walter H, Steinbach-Rankins Jill M
Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, KY, United States; Center for Predictive Medicine, Louisville, KY, United States.
Department of Biochemistry, School of Medicine, University of Louisville, KY, United States.
Int J Pharm. 2017 Oct 5;531(1):118-133. doi: 10.1016/j.ijpharm.2017.08.061. Epub 2017 Aug 7.
Sexually transmitted infections affect hundreds of millions of people worldwide. Both human immunodeficiency virus (HIV-1 and -2) and herpes simplex virus-2 (HSV-2) remain incurable, urging the development of new prevention strategies. While current prophylactic technologies are dependent on strict user adherence to achieve efficacy, there is a dearth of delivery vehicles that provide discreet and convenient administration, combined with prolonged-delivery of active agents. To address these needs, we created electrospun fibers (EFs) comprised of FDA-approved polymers, poly(lactic-co-glycolic acid) (PLGA) and poly(DL-lactide-co-ε-caprolactone) (PLCL), to provide sustained-release and in vitro protection against HIV-1 and HSV-2. PLGA and PLCL EFs, incorporating the antiretroviral, tenofovir disoproxil fumarate (TDF), exhibited sustained-release for up to 4 weeks, and provided complete in vitro protection against HSV-2 and HIV-1 for 24h and 1 wk, respectively, based on the doses tested. In vitro cell culture and EpiVaginal tissue tests confirmed the safety of fibers in vaginal and cervical cells, highlighting the potential of PLGA and PLCL EFs as multipurpose next-generation drug delivery vehicles.
性传播感染影响着全球数亿人。人类免疫缺陷病毒（HIV-1和HIV-2）以及单纯疱疹病毒2型（HSV-2）仍然无法治愈，这促使人们开发新的预防策略。虽然目前的预防技术依赖于使用者严格遵守以实现疗效，但缺乏能够提供隐秘、便捷给药方式，并能延长活性剂释放时间的给药载体。为满足这些需求，我们制备了由美国食品药品监督管理局（FDA）批准的聚合物聚乳酸-乙醇酸共聚物（PLGA）和聚（DL-丙交酯-ε-己内酯）（PLCL）组成的电纺纤维（EFs），以提供针对HIV-1和HSV-2的缓释和体外保护。含有抗逆转录病毒药物富马酸替诺福韦二吡呋酯（TDF）的PLGA和PLCL电纺纤维显示出长达4周的缓释效果，并且根据测试剂量，分别为HSV-2和HIV-1提供了24小时和1周的完全体外保护。体外细胞培养和阴道上皮组织测试证实了纤维在阴道和宫颈细胞中的安全性，凸显了PLGA和PLCL电纺纤维作为多功能下一代给药载体的潜力。
