Development of surface modified nanoparticles of curcumin for topical treatment of diabetic retinopathy: In vitro, ex vivo and in vivo investigation

Abstract

Diabetic retinopathy (DR) is the worst microvascular complication of diabetes that results in blindness. Present treatment of DR is invasive and associated with pain and inflammation. There is a need to develop painless treatment. The surface-modified PLGA (50:50) nanoparticles of Curcumin, which is a peroxisome proliferator-activated receptor-gamma agonist, were prepared to target DR by topical administration. Nanoparticles were optimized by a 32 factorial design. The Concentration of PLGA and number of HPH cycles at fixed pressure were independent variables whereas particle size. PDI and % entrapment efficiency were the dependent variables. Batch F6 with particle size, PDI, and % EE 194.7 nm, 0.231, and 90% respectively was selected as the optimized batch. The optimized batch was further subjected to spray drying and evaluated for various parameters. Residual solvent analysis was carried out by Gas chromatography. In vitro drug release study showed a biphasic drug release pattern of 70.17 ± 1.38% cumulative drug release at the end of 10 h. The release profile of curcumin from nanoparticles appeared to fit best with the Higuchi model. XRD study confirmed the molecular dispersion of the drug. The formulation showed satisfactory results in sterility testing, histology and isotonicity testing. In vivo study on rats showed dose dependent reduction in vascular endothelial growth factor (VEGF) concentration in vitreous fluid. Based on available evidences it can be concluded that the prepared formulation possesses great potential to manage diabetic retinopathy.