Trimethyl chitosan-hyaluronic acid nano-polyplexes for intravitreal VEGFR-2 siRNA delivery: Formulation and in vivo efficacy evaluation.
Chitosan
/ chemistry
Choroidal Neovascularization
/ drug therapy
Drug Compounding
Drug Delivery Systems
Human Umbilical Vein Endothelial Cells
Humans
Hyaluronic Acid
/ chemistry
Intravitreal Injections
RNA, Small Interfering
/ chemistry
Vascular Endothelial Growth Factor Receptor-2
/ antagonists & inhibitors
Choroidal neovascularization
Laser induced CNV
Ocular delivery
Tri methyl chitosan-hyaluronic acid nano-polyplex
VEGFR-2 siRNA
Journal
Nanomedicine : nanotechnology, biology, and medicine
ISSN: 1549-9642
Titre abrégé: Nanomedicine
Pays: United States
ID NLM: 101233142
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
11
09
2019
revised:
06
01
2020
accepted:
26
02
2020
pubmed:
15
3
2020
medline:
1
6
2021
entrez:
15
3
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32169399
pii: S1549-9634(20)30033-2
doi: 10.1016/j.nano.2020.102181
pii:
doi:
Substances chimiques
RNA, Small Interfering
0
Hyaluronic Acid
9004-61-9
Chitosan
9012-76-4
Vascular Endothelial Growth Factor Receptor-2
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
102181Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.