Drug repositioning is an important drug development strategy as it saves the time and efforts exerted in drug discovery. Since reepithelization of the cornea is a critical problem, we envisioned that the
anticonvulsant phenytoin sodium can promote reepithelization of corneal
ulcers as it was repurposed for skin wound healing. Herein, our aim is to develop novel
crown ether-based nanovesicles "Crownsomes" of
phenytoin sodium for ocular delivery with minimal drug-induced irritation and enhanced efficacy owing to "host-guest" properties of
crown ethers. Crownsomes were successfully fabricated using span-60 and
18-crown-6 and their size, morphology, polydispersity index, ΞΆ potential, drug loading efficiency, conductivity, and drug release were characterized. Crownsomes exhibited favorable properties such as formation of spherical nanovesicles of 280 ± 18 nm and -26.10 ± 1.21 mV surface charges. Crownsomes depicted a high entrapment efficiency (77 ± 5%) with enhanced and controlled-release pattern of
phenytoin sodium. The optimum crownsomes formulation ameliorated ex vivo corneal drug permeability (1.78-fold than drug
suspension) through the corneal
calcium extraction ability of
18-crown-6. In vivo study was conducted utilizing an
alkali-induced
corneal injury rabbit model. Clinical and histopathological examination confirmed that crownsomes exhibited better biocompatibility and minimal irritation due to complex formation and drug shielding. Further, they enhanced corneal healing, indicating their effectiveness as a novel drug delivery system for ocular diseases.