Journal
INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume 14, Issue -, Pages 45-55Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S184574
Keywords
ICNPH; diabetic retinopathy; subconjunctival injection; insulin delivery; thermo-sensitive hydrogel; PLGA-PEG-PLGA hydrogel
Funding
- National Natural Science Foundation of China [813008068, 81570842, 81770907, 81470613, 81100653, 81670835, 81270989]
- Shanghai High Myopia Study Group
- International Science and Technology Cooperation Foundation of Shanghai [14430721100]
- Shanghai Talent Development Fund [201604]
- Shanghai Youth Doctor Support Program [2014118]
- Outstanding Youth Medical Talents Program of Shanghai Health and Family Planning Commission [2017YQ011]
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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.
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