Trimethyl Chitosan-Hyaluronic Acid Nano-Polyplexes for Intravitreal Vegfr-2 Sirna Delivery: Formulation and in Vivo Efficacy Evaluation Publisher Pubmed



Chaharband F¹ ; Daftarian N² ; Kanavi MR³ ; Varshochian R⁴ ; Hajiramezanali M⁴ ; Norouzi P¹ ; Arefian E⁵ ; Atyabi F^{1, 4, 6} ; Dinarvand R^{4, 6} Show Affiliations
Source: Nanomedicine: Nanotechnology# Biology# and Medicine Published:2020

Abstract

As vascular endothelial growth factor in choroidal neovascularization is a major cause of visual loss of the elderlies and diabetics, gene therapy may offer an alternative treatment. However, siRNA instability and inefficient delivery are the main hindrances. To address this issue, we developed a nano-sized siRNA loaded therapeutic delivery system. The chitosan-hyaluronic acid nano-polyplexes were prepared by the modified ionic gelation method. The obtained nano-polyplex with a narrow size distribution, indicated no significant cytotoxicity in the MTT test and proper cellular uptake in confocal images. The RT-PCR analysis indicated remarkable gene silencing on HUVEC cells. The intravitreally administered nano-polyplexes in rabbits overcame both the vitreous and retina barriers and reached the posterior tissues efficiently. Intravitreal injections of the VEGFR-2 siRNA nano-polyplexes significantly reduced the size of the laser-induced choroidal neovascularization, compared to the control group. Consequently, the developed formulation can be a promising candidate for intravitreal delivery of siRNA. © 2020 Elsevier Inc.