Naringenin and quercetin nanoparticles as a dual strategy for topical management of diabetic retinopathy

Abstract

Diabetic retinopathy (DR) is a complication associated with diabetes that impacts the retinal microvasculature and leads to vision problems. The currently available treatments for diabetic retinopathy are invasive and associated with pain and side effects, which lead to patient noncompliance. This research aims to formulate nanoparticles of two PPAR-γ agonists, viz. quercetin and naringenin, by using two different polymers, as HPMC-Poloxamer and PLGA, respectively. For optimization, a 3² Factorial design was used. The HPH pressure and PLGA concentration were independent variables for naringenin nanoparticles; Poloxamer concentration and HPH pressure were independent variables for quercetin nanoparticles. The particle size, PDI, and entrapment efficiency were the responses. The optimized batch of naringenin showed a particle size of 187.1 nm, PDI 0.117, and percent entrapment of 91 %, whereas the optimized quercetin batch showed a particle size of 185 nm, PDI 0.289, and 82.5 % entrapment. The optimized batch was further subjected to spray drying and characterized by various in-vitro, ex-vivo, and in-vivo methods. Nanoparticles showed spherical shape with smooth morphology in the SEM study, and XRD confirmed the entrapment of both drugs in the selected polymers. In vitro drug release study showed the comparatively rapid drug release of quercetin (90.55 ± 0.972 %) and more sustained drug release of naringenin (48.90 ± 0.894 %) at the end of 10 h. Differences in the release of drugs are characteristic of particular polymers used during preparation. This will prevent competition between two drugs to bind to receptors. Results from the isotonicity study, ex-vivo examination indicate the non-irritant nature and safety of the formulation. The in-vivo study on Wistar rats suggests formulation containing a combination of nanoparticles showed a synergistic effect in reducing VEGF, an important factor in diabetic retinopathy, than the individual treatment with nanoparticles of the particular drug. The study finding suggests that treatment with a combination of nanoparticles of quercetin and naringenin prepared by two different polymers having different drug release patterns can be considered as an alternate non-invasive therapy approach for the treatment of diabetic retinopathy.