Department of Pharmaceutics, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, University of Mumbai, V.M.Road, Vile Parle West, Mumbai, Maharashtra, 400056, India.
Department of Biochemistry and Virology, ICMR National Institute for Research in Reproductive Health, Govt. India, Mumbai, Maharashtra, India.
Drug Deliv Transl Res. 2020 Aug;10(4):962-974. doi: 10.1007/s13346-020-00741-4.
Increasing incidences of sexually transmitted disease including human papillomavirus (HPV), herpes simplex virus (HSV), and human immunodeficiency virus (HIV) infection in women have triggered the need for developing user-friendly potential prophylactic approach. Presently, although several therapeutic moieties are in place but none of them have prophylactic action, they are confined to provide symptomatic relief to the patient-researchers which have now recognized the need for discovering efficient topical prophylactic agents. One of these with great potential topical microbicide uncovered is vaginal delivery of small interfering RNA (siRNA). siRNA delivery involves silencing gene expression in a sequence specific manner in causative agent thereby exhibiting microbicide activity. However, the mucosal barrier and physiological changes in vagina such as pH and variable epithelial layer thickness during menstrual cycle serve as major hurdles for efficient delivery and cellular uptake of siRNA. In order to enhance vaginal delivery of siRNA, nanocarrier systems like lipid-based delivery systems, macromolecular systems, polymeric nanoparticles, aptamer and cell-penetrating peptides have been investigated widely until date. The present article elaborates on various nanocarriers and their promising outcomes at preclinical stage and future implications of nanocarrier-based siRNA vaginal delivery. Graphical abstract Overview on barriers to the delivery of siRNA by vaginal route and nanocarrier envisaged until date for enhancing efficient delivery of siRNA.
女性的性传播疾病（包括人乳头瘤病毒（HPV）、单纯疱疹病毒（HSV）和人类免疫缺陷病毒（HIV）感染）发病率不断上升，这促使人们需要开发用户友好的潜在预防方法。目前，尽管有几种治疗药物已经问世，但它们都没有预防作用，只能为患者提供对症缓解。现在研究人员已经认识到需要发现有效的局部预防药物。其中一种具有很大潜力的局部杀微生物剂是阴道递送人源小干扰 RNA（siRNA）。siRNA 递送人源小干扰 RNA（siRNA）通过序列特异性沉默靶基因的表达，从而表现出杀微生物活性。然而，黏膜屏障和阴道中的生理变化，如 pH 值和月经周期中上皮层厚度的变化，是有效递送和细胞摄取 siRNA 的主要障碍。为了增强 siRNA 的阴道递送，脂质体等纳米载体系统、高分子系统、聚合物纳米粒子、适体和穿透肽已被广泛研究。本文详细介绍了各种纳米载体及其在临床前阶段的有前途的结果，以及基于纳米载体的 siRNA 阴道递送的未来意义。
图摘要通过阴道途径递送 siRNA 的障碍概述和迄今为止用于增强 siRNA 有效递送的纳米载体设想。
