Vaginal siRNA delivery: overview on novel delivery approaches
Vaginal siRNA delivery: overview on novel delivery approaches
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DOI：
10.1007/s13346-020-00741-4
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发表时间：
2020-08-01
影响因子：
5.4
通讯作者：
Fernandes, Trinette
中科院分区：
文献类型：
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作者：
Baxi, Krishna;Sawarkar, Sujata;Fernandes, Trinette
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）感染的妇女发病率不断上升，引发了需要开发用户友好的潜在预防方法。目前，虽然有几种治疗部分，但它们都没有预防作用，它们仅限于为患者提供症状缓解-研究人员现在已经认识到需要发现有效的局部预防剂。其中一个具有巨大潜力的局部杀微生物剂是阴道递送小干扰RNA（siRNA）。siRNA递送涉及在病原体中以序列特异性方式沉默基因表达，从而表现出杀微生物剂活性。然而，阴道中的粘膜屏障和生理变化（例如，月经周期期间的pH和可变的上皮层厚度）是siRNA的有效递送和细胞摄取的主要障碍。为了增强siRNA的阴道递送，迄今为止已经广泛研究了纳米载体系统如基于脂质的递送系统、大分子系统、聚合物纳米颗粒、适体和细胞穿透肽。本文阐述了各种纳米载体及其在临床前阶段的前景和基于纳米载体的siRNA阴道递送的未来意义。概述了通过阴道途径递送siRNA的障碍和迄今为止设想的用于增强siRNA有效递送的纳米载体
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.Overview on barriers to the delivery of siRNA by vaginal route and nanocarrier envisaged until date for enhancing efficient delivery of siRNA