Corneal chemical burn treatment through a delivery system consisting of TGF-β1 siRNA: in vitro and in vivo

Corneal chemical burn treatment through a delivery system consisting of TGF-β1 siRNA: in vitro... Chemical burns are major causes of corneal blindness. Transforming growth factor beta-1 (TGFβ ) plays an important role in induction of corneal inflammation-related-fibrosis leading to the blindness. Here, a topical delivery system consisting anti- fibrotic TGF-β siRNA, an inflammatory suppressing gene, was designed for treatment of corneal injuries. TGF-β siRNA 1 1 loaded in nanoparticles (NPs) made up of polyethyleneimine polymer demonstrated high fibroblast transfection efficiency. Moreover, TGF-β and PDGF genes and ECM deposition were suppressed in isolated human corneal fibroblasts. NPs inhibited proliferation and transformation of fibroblasts to myofibroblasts by S-phase arrest and α-SMA suppression in vitro, respectively. The mentioned finding was also confirmed in vivo, addressing high wound-healing potential of prepared gene delivery system which was superior to conventional betamethasone treatment. Besides, CD4 and α-SMA antibody staining showed inhibited angiogenesis and myofibroblast accumulation in treated corneas. This study opens a new way for treating corneal fibrosis through topical siRNA delivery. . . . . Keywords TGF-β siRNA Polyethyleneimine Angiogenesis Myofibroblasts Corneal haze Introduction membrane, leading to corneal blindness [1, 2]. Considering the severity of injury, corneal alkaline burns are graded into Chemical injuries to the eye (cornea and conjunctiva) can pro- four groups. Alkaline-burned corneas seldom heal http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Drug Delivery and Translational Research Springer Journals

Corneal chemical burn treatment through a delivery system consisting of TGF-β1 siRNA: in vitro and in vivo

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Publisher
Springer US
Copyright
Copyright © 2018 by Controlled Release Society
Subject
Biomedicine; Pharmaceutical Sciences/Technology
ISSN
2190-393X
eISSN
2190-3948
D.O.I.
10.1007/s13346-018-0546-0
Publisher site
See Article on Publisher Site

Abstract

Chemical burns are major causes of corneal blindness. Transforming growth factor beta-1 (TGFβ ) plays an important role in induction of corneal inflammation-related-fibrosis leading to the blindness. Here, a topical delivery system consisting anti- fibrotic TGF-β siRNA, an inflammatory suppressing gene, was designed for treatment of corneal injuries. TGF-β siRNA 1 1 loaded in nanoparticles (NPs) made up of polyethyleneimine polymer demonstrated high fibroblast transfection efficiency. Moreover, TGF-β and PDGF genes and ECM deposition were suppressed in isolated human corneal fibroblasts. NPs inhibited proliferation and transformation of fibroblasts to myofibroblasts by S-phase arrest and α-SMA suppression in vitro, respectively. The mentioned finding was also confirmed in vivo, addressing high wound-healing potential of prepared gene delivery system which was superior to conventional betamethasone treatment. Besides, CD4 and α-SMA antibody staining showed inhibited angiogenesis and myofibroblast accumulation in treated corneas. This study opens a new way for treating corneal fibrosis through topical siRNA delivery. . . . . Keywords TGF-β siRNA Polyethyleneimine Angiogenesis Myofibroblasts Corneal haze Introduction membrane, leading to corneal blindness [1, 2]. Considering the severity of injury, corneal alkaline burns are graded into Chemical injuries to the eye (cornea and conjunctiva) can pro- four groups. Alkaline-burned corneas seldom heal

Journal

Drug Delivery and Translational ResearchSpringer Journals

Published: Jun 4, 2018

References

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