Design and evaluation of curcumin, naringenin, and alpha-lactalbumin encapsulated nanostructured lipid carriers for targeted ocular drug delivery in diabetic retinopathy.

Diabetic retinopathy (DR), a leading cause of vision impairment and blindness, poses significant challenges for ocular drug delivery due to barriers limiting drug penetration to the eye's posterior segment. This study aimed to develop and characterize nanostructured lipid carriers (NLCs) encapsulating curcumin, naringenin, and alpha-lactalbumin for sustained and targeted ocular delivery via topical administration in DR management. The NLCs exhibited a uniform particle size of 138.7 ± 2.6 nm, high encapsulation efficiency (∼97 %), and a stable zeta potential of -25.6 mV. Transmission electron microscopy confirmed their spherical morphology, and differential scanning validated successful drug incorporation. In vitro studies demonstrated sustained release (82-86 % over 24 h), while ex vivo trans-corneal permeation using goat corneas showed effective drug penetration (67-73 % within 12 h). In vivo efficacy was assessed in a diabetic rat model over four weeks, where NLC-treated groups showed significant reduction in rat vitreous VEGF levels and preserved retinal morphology without signs of edema or hemorrhage. The NLC-based eye drop formulation demonstrated sustained drug release, enhanced trans-corneal drug permeation, and a significant reduction in vitreous VEGF levels, offering a promising, non-invasive therapeutic strategy for diabetic retinopathy and other posterior segment ocular disorders. Although retinal drug concentrations were not quantified in this study, pharmacodynamic outcomes support the formulation's potential efficacy; future studies will include pharmacokinetic profiling to further substantiate these findings.