Journal
MOLECULAR PHARMACEUTICS
Volume 17, Issue 10, Pages 3952-3965Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.0c00742
Keywords
18-crown-6; crownsomes; corneal ulcer; drug repurposing; phenytoin sodium; Span 60
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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,. 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.
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