Biodegradable Film for the Targeted Delivery of siRNA-Loaded Nanoparticles to Vaginal Immune Cells
- 6 July 2015
- journal article
- research article
- Published by American Chemical Society (ACS) in Molecular Pharmaceutics
- Vol. 12 (8), 2889-2903
- https://doi.org/10.1021/acs.molpharmaceut.5b00073
Abstract
The goal of this study was to develop and characterize a novel intravaginal film platform for targeted delivery of small interfering RNA (siRNA)-loaded nanoparticles (NP) to dendritic cells as a potential gene therapy for the prevention of sexually transmitted human immunodeficiency virus (HIV) infection. Poly(ethylene glycol) (PEG)-functionalized poly(D, L-lactic-co-glycolic acid) (PLGA)/polyethylenimine (PEI)/siRNA NP (siRNA-NP) were fabricated using a modified emulsion-solvent evaporation method and characterized for particle size, zeta potential, encapsulation efficiency (EE), and siRNA release. siRNA-NP were decorated with anti-HLA-DR antibody (siRNA-NP-Ab) for targeting delivery to HLA-DR+ dendritic cells (DCs) and homogeneously dispersed in a biodegradable film consisting of poly vinyl alcohol (PVA) and λ-carrageenan. The siRNA-NP-Ab-loaded film (siRNA-NP-Ab-film) was transparent, displayed suitable physicomechanical properties, and was noncytotoxic. Targeting activity was evaluated in a mucosal coculture model consisting of a vaginal epithelial monolayer (VK2/E6E7 cells) and differentiated KG-1 cells (HLA-DR+ DCs). siRNA-NP-Ab were rapidly released from the film and were able to penetrate the epithelial layer to be taken up by differentiated KG-1 cells. siRNA-NP-Ab demonstrated higher targeting activity and significantly higher knockdown of synaptosome-associated 23-kDa protein (SNAP-23) mRNA and protein when compared to siRNA-NP without antibody conjugation. Overall, these data suggest that our novel siRNA-NP-Ab-film may be a promising platform for preventing HIV infection within the female genital tract.Keywords
Funding Information
- Manitoba Health Research Council
This publication has 43 references indexed in Scilit:
- Development of polyether urethane intravaginal rings for the sustained delivery of hydroxychloroquineDrug Design, Development and Therapy, 2014
- Silencing Sexually Transmitted Infections: Topical siRNA-Based Interventions for the Prevention of HIV and HSVInfectious Diseases in Obstetrics and Gynecology, 2014
- Vaginal Delivery of Paclitaxel via Nanoparticles with Non‐Mucoadhesive Surfaces Suppresses Cervical Tumor GrowthAdvanced Healthcare Materials, 2013
- Advancements in the field of intravaginal siRNA deliveryJournal of Controlled Release, 2013
- Mucus-Penetrating Nanoparticles for Vaginal Drug Delivery Protect Against Herpes Simplex VirusScience Translational Medicine, 2012
- Vaginal delivery of siRNA using a novel PEGylated lipoplex-entrapped alginate scaffold systemJournal of Controlled Release, 2011
- Mucoadhesive Vaginal Drug Delivery SystemsRecent Advances in Drug Delivery and Formulation, 2009
- Vaginal Drug Delivery Systems for HIV PreventionThe AAPS Journal, 2009
- Durable Protection from Herpes Simplex Virus-2 Transmission Following Intravaginal Application of siRNAs Targeting Both a Viral and Host GeneCell Host & Microbe, 2009
- T Cell-Specific siRNA Delivery Suppresses HIV-1 Infection in Humanized MiceCell, 2008