Vaginal siRNA delivery: overview on novel delivery approaches

Abstract

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.

Keywords: Nanocarriers; Sexually transmitted disease; Topical microbicide; Vaginal; siRNA.