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, ζ 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.