Trimethyl chitosan-hyaluronic acid nano-polyplexes for intravitreal VEGFR-2 siRNA delivery: Formulation and in vivo efficacy evaluation

• Published in: Nanomedicine Vol. 26; p. 102181
• Main Authors: Chaharband, Farkhondeh, Daftarian, Narsis, Kanavi, Mozhgan Rezaei, Varshochian, Reyhaneh, Hajiramezanali, Maliheh, Norouzi, Parisa, Arefian, Ehsan, Atyabi, Fatemeh, Dinarvand, Rassoul
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-06-2020
• Subjects: Choroidal neovascularization; Laser induced CNV; Ocular delivery; Tri methyl chitosan-hyaluronic acid nano-polyplex; VEGFR-2 siRNA; AS-ODNs; Tri methyl chitosan-hyaluronic acid nano-polyplex; IVT; RPE; Laser induced CNV; CNV; MTT; siRNAs; DMEM; MFI; PDI; Ocular delivery; RT-PCR; FBS; AMD; HUVEC; Choroidal neovascularization; VEGF; FESEM; TMC; NRP 1; NPs; NMP; NMR; BRB; PEG; VEGFR-2 siRNA; HA
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2020.102181

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.
The TMC-HA nano-polyplexes were successfully developed by the modified ionic gelation method. The obtained nano-polyplexes show appropriate cellular uptake in confocal images on the HUVEC and RPE cell lines. Furthermore, the intravitreally injected nano-polyplexes in rabbits eyes overcame both the vitreous and retina barriers and reached the posterior tissues efficiently. [Display omitted]