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Neuroprotective effect of insulin-loaded chitosan nanoparticles/PLGA-PEG-PLGA hydrogel on diabetic retinopathy in rats

Authors Rong X, Ji Y, Zhu X, Yang J, Qian D, Mo X, Lu Y

Received 20 August 2018

Accepted for publication 27 November 2018

Published 18 December 2018 Volume 2019:14 Pages 45—55

DOI https://doi.org/10.2147/IJN.S184574

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Alexander Kharlamov

Peer reviewer comments 4

Editor who approved publication: Dr Linlin Sun


Xianfang Rong,1–5 Yinghong Ji,1–5 Xiangjia Zhu,1–5 Jin Yang,1–5 Dongjin Qian,1–5 Xiaofen Mo,1–5 Yi Lu1–5

1Department of Ophthalmology and The Eye Institute, Eye and Ear, Nose, and Throat Hospital, Fudan University, Shanghai, China; 2The Key Laboratory of Myopia, Ministry of Health, Shanghai, China; 3Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China; 4Key National Health Committee Key Laboratory of Myopia, Fudan University, Shanghai, China; 5Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China

Background: To pursuit effective sustained release systems for insulin to treat diabetic retinopathy (DR), a novel insulin delivering system was developed via loading onto chitosan nanoparticles/poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid) hydrogel (ICNPH).
Methods and materials: Examinations including electroretinography, HE staining, transmission electron microscopy, terminal deoxynucleotidyl transferased UTP nick-end labeling, immunofluorescence, Western blot, and real-time polymerase chain reaction were performed to evaluate the neuroprotective efficacy of ICNPH on DR by a single subconjunctival injection.
Results: Compared with the insulin, blank, and sham treatment groups, subconjunctival injection of ICNPH significantly reduced the decrease of scotopic B-wave amplitude, alleviated retinal micro- and ultrastructural changes, and reduced retinal cell apoptosis caused in DR rats. Meanwhile, a significant reduction of vascular endothelial growth factor and glial fibrillary acidic protein expression as well as a remarkable increase in Occludin expression was also found in retinas in ICNPH group compared with the sham treatment group.
Conclusion: The results indicate that ICNPH has sufficient neuroprotective effect on retinas through subconjunctival injection in DR rats and facilitates controlled insulin delivery. It might be one of the therapeutic strategies for DR in the near future.

Keywords:
ICNPH, diabetic retinopathy, subconjunctival injection, insulin delivery, thermosensitive hydrogel, PLGA-PEG-PLGA hydrogel

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