Topical Temperature-sensitive Gel Containing DsiRNA-chitosan Nanoparticles for Potential Treatment of Skin Cancer

Abstract

Background: Target specific delivery of RNA interference (RNAi)-based molecules against Vascular Endothelium Growth Factor (VEGF) has been regarded as a promising approach in skin cancer therapy like melanoma. Chitosan (CS) nanoparticles have been extensively studied for efficient delivery of RNAi-based molecules such as small interfering RNA (siRNA) and Dicer-substrate RNA (DsiRNA). Material(s) and Method(s): The CS nanoparticles were prepared via ionic gelation method prior to DsiRNA adsorption. The DsiRNA-loaded CS nanoparticles were later incorporated into PF-127 (25 and 30% w/v) to form temperature-sensitive gels to facilitate their delivery through the skin barrier. The gels were later subject to rheology, FTIR, scanning electron microscopy analysis and gelation temperature as well as drug release determination. Result(s): Particle size of the resultant DsiRNA-loaded CS nanoparticles ranged from 146.0+/-19.3 to 217.7+/-20.5 nm with variable encapsulation efficiency (81.8+/-1.8 to 90.1+/-1.8%), depending on CS concentration. The gel (PF-127 25% w/v) containing DsiRNA-loaded CS nanoparticles had the desired viscosity (0.751+/-0.005 to 0.839+/-0.04 Pa sec) as well as gelation temperature (24.3+/-0.6 to 25.3+/-0.6) and exhibited a sustained drug release for almost 7 days. Conclusion(s): A temperature-sensitive gel containing DsiRNA-loaded CS nanoparticles was successfully developed and it has a potential to be further developed as a gene delivery system for skin cancer therapy.Copyright © 2017 Haliza Katas et al.