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

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.

How can nanotechnology help to combat COVID-19? Opportunities and urgent need

“…In order to both reduce the treatment costs and streamline the production, Testori suggests the use of plasmids as engineered vectors to produce interleukin (IL)-10 inside cells to contain the inflammatory process [ 142 ]. Nanoparticles made of polyethylenimine (PEI) [ 143 ], PLGA [ 144 ] PEG-PCL [ 145 ], PLA-PEG [ 146 ] and so on have been successfully studied with regard to the systematic delivery of interleukins as immunotherapy for different types of diseases, and these findings could be helpful in the development of efficient nanoparticle therapies for cytokine storm in patients with COVID-19.…”

The Use of Polymer Blends in the Treatment of Ocular Diseases

“…In another study aiming at the treatment of diabetic retinopathy, Zeng and collaborators (2019) developed PLGA/chitosan nanoparticles containing interleukin-2, a cytokine with anti-angiogenic and antitumor efficacy. Despite the moderate drug encapsulation efficacy (34.7%), the formulation showed sustained drug release, with a strong anti-angiogenic effect and significantly lower cytokine expression after the intravitreal injection, compared to an interleukin-2 solution [ 174 ]. Similarly, Mahaling et al, 2018, evaluated nanoparticle eye drops consisting of a polycaprolactone core and Pluronic ® F68 shell, loaded with triamcinolone acetonide.…”

Vascular restenosis reduction with platelet membrane coated nanoparticle directed M2 macrophage polarization

“…A repeated freeze-thaw process was performed to extract the platelet membrane ( Hu et al., 2015 ). IL10-NPs were prepared by a modified double solvent evaporation method as previously described with slight modification ( Zeng et al., 2019 ). In brief, 1 mL of PLGA (Sigma-Aldrich, USA) solution in ethyl acetate (60 mg/mL) was mixed with recombinant rat IL10 (Abcam, Cambridge, UK) and D- (+)-glucosamine (4 and 6 w/w % of total PLGA mass) dissolved in 100 μL ultrapure DNase/RNase-free distilled water.…”