Core-shell nanotherapeutics for diabetic cataract and retinopathy: current state-of-the-art and translational challenges.

Diabetes associated ocular complications, such as diabetic retinopathy (DR) and diabetic cataract (DC), constitute a substantial number of blind cases worldwide. Contemporary therapeutic interventions include intravitreal administration of anti-VEGF drugs for DR and surgical interventions for DC. However, these interventions suffer from drawbacks such as low patient compliance, invasiveness, and elicitation of unintended effects on sensitive ocular tissues, ultimately leading to vision loss. Therefore, there is a need for the development of advanced therapeutic interventions that are less invasive. The advent of nanotechnology has brought a paradigm shift in the treatment of ophthalmic diseases, including DR and DC. Nanoparticles, due to their high aspect ratio, offer several advantages such as quick internalization, ease of surface modification, and amenability for attachment of targeting ligands, thereby offering improved bioavailability. Moreover, the development of core-shell nanoparticles, with varying surface and bulk composition, offers additional advantages such as tissue tropism, controlled drug release, stimuli-responsiveness, and amenability for multiple drug loading, improved stability, permeability, and intra-ocular accumulation while showing minimal toxicity, ultimately offering spatio-temporally controlled drug delivery. In this review, we discussed various ocular tissue barriers while emphasizing the importance of different pristine and core-shell polymeric nanoparticles with respect to tissue tropism. Further, characterization techniques and drug release mechanisms of core-shell nanoparticles were discussed. We also presented preclinical studies that demonstrated improved therapeutic efficacy of nanoparticulate delivery systems. Finally, we presented our perspectives on challenges for scale-up and clinical translation of core-shell nanoparticles.