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

Abstract

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.

• Authors: Lina Zeng, Wenbei Ma, Lingyu Shi, Xiaohong Chen, Rong Wu, Yingying Zhang, Huaiwen Chen, Hui Chen
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 14 Pg. 6357-6369 ( 2019) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 31496691 (Publication Type: Journal Article)

Chemical References

• Delayed-Action Preparations
• Vascular Endothelial Growth Factor A
• Interleukin-12
• Polylactic Acid-Polyglycolic Acid Copolymer
• Matrix Metalloproteinase 9

Topics

• Animals
• Delayed-Action Preparations (pharmacology)
• Diabetic Retinopathy (drug therapy, pathology)
• Drug Delivery Systems
• Endothelial Cells (metabolism)
• Interleukin-12 (administration & dosage, therapeutic use)
• Intravitreal Injections
• Male
• Matrix Metalloproteinase 9 (metabolism)
• Mice
• Nanoparticles (chemistry, ultrastructure)
• Neovascularization, Pathologic (drug therapy)
• Polylactic Acid-Polyglycolic Acid Copolymer (chemistry)
• Rats, Sprague-Dawley
• Retina (drug effects, metabolism, pathology)
• Vascular Endothelial Growth Factor A (metabolism)