Back to Journals » International Journal of Nanomedicine » Volume 14

Poly(lactic-co-glycolic acid) nanoparticle-mediated interleukin-12 delivery for the treatment of diabetic retinopathy

Authors Zeng L, Ma W, Shi L, Chen X, Wu R, Zhang Y, Chen H, Chen H

Received 7 May 2019

Accepted for publication 16 July 2019

Published 8 August 2019 Volume 2019:14 Pages 6357—6369

DOI https://doi.org/10.2147/IJN.S214727

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Alexander Kharlamov

Peer reviewer comments 2

Editor who approved publication: Dr Mian Wang


Lina Zeng,1,* Wenbei Ma,1,* Lingyu Shi,1 Xiaohong Chen,1 Rong Wu,1 Yingying Zhang,2 Huaiwen Chen,2 Hui Chen1

1Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, People’s Republic of China; 2Sunlipo Biotech Research Center for Nanomedicine, Shanghai 201507, People’s Republic of China

*These authors contributed equally to this work

Background: Diabetic retinopathy (DR) is a complication of diabetes that affects the eyes and vision. It is a leading cause of visual impairment and blindness in working-age people. Vascular endothelial growth factor-A (VEGF-A) is a primary initiator and potential mediator of DR. Matrix metalloproteinase-9 (MMP-9) plays a progressive role in the onset and severity of DR. Interleukin-12 (IL-12) is a cytokine of the chemokine family that could reduce the levels of MMP-9 and VEGF-A and suppress tumor angiogenesis. We hypothesize that IL-12 may also have superior therapeutic efficacy against DR. However, protein drugs are prone to degradation by various proteases after drug injection. Therefore, they have short half-lives and low blood concentrations. The objective of this study was to develop IL-12-loaded nanoparticles for long-term and sustained DR treatment.
Methods: IL-12-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (IL-12-PNP) were developed by double emulsion. The characteristics, anti-DR activity, and mechanisms of IL-12-PNP were examined in vitro and in vivo.
Results: The nanoparticles had suitable particle size (∼132.8 nm), drug encapsulation efficiency (∼34.7%), and sustained drug release profile. Compared with IL-12 and blank nanoparticles, IL-12-PNP showed better inhibitory efficacy against VEGF-A and MMP-9 expression in rat endothelial cells and DR mouse retina. Intraocular IL-12-PNP administration significantly reduced retinal damage in DR mice as they presented with increased thickness and decreased neovascularization after treatment.
Conclusion: These data indicate that IL-12-PNP is an effective drug delivery platform for DR therapy. It restores the thickness and reduces neovascularization of the retinas of DR mice.

Keywords: interleukin-12, nanoparticles, angiogenesis, controlled release, diabetic retinopathy

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]