Voriconazole Composited Polyvinyl Alcohol/Hydroxypropyl-β-Cyclodextrin Nanofibers for Ophthalmic Delivery.

Xiaoyi Sun,Zhenwei Yu,Lingyan Yu,Zhengyuan Cai,Yuanyuan Lv,Bing Xu

doi:10.1371/journal.pone.0167961

Xiaoyi Sun, Zhenwei Yu + Show 4 more

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https://doi.org/10.1371/journal.pone.0167961

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Abstract

Voriconazole (VRC) incorporated in composited polyvinyl alcohol (PVA)/hydroxypropyl-β-cyclodextrin (HPβCD) blended nanofibers were produced via electrospinning for efficient ophthalmic delivery. The VRC loading capacity increased with increasing HPβCD content. The optimal solution for electrospinning consisted of 8% (w/v) PVA, 4% (w/v) HPβCD and 0.5% (w/v) VRC. The nanofibers exhibited bead-free average fiber diameters of 307±31 nm and VRC was released in vitro in a sustained manner. The VRC nanofibers were characterized by infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The proton nuclear magnetic resonance (1H-NMR) was used to analyze the molar ratio of HPβCD/VRC in the nanofibers. Compared with a VRC solution, the nanofibers significantly prolonged the half life, and increased the bioavailability of VRC in rabbit tears. No obvious signs of irritation were observed after application in the conjunctival sac. VRC nanofibers are promising for ophthalmic drug delivery and further pharmacodynamics studies are needed.

Highlights

Fungal keratitis, a fungal infection of the cornea, is one of the most serious ocular fungal infections
With the extensive application of broad-spectrum antibiotics and corticosteroids, the incidence of fungal keratitis has increased recently. It has become the major cause of blindness caused by ocular fungal infections [1, 2]
The lack of specificity of antifungal agents is the main obstacle to successful therapy [3]

Summary

Introduction

A fungal infection of the cornea, is one of the most serious ocular fungal infections. With the extensive application of broad-spectrum antibiotics and corticosteroids, the incidence of fungal keratitis has increased recently It has become the major cause of blindness caused by ocular fungal infections [1, 2]. Voriconazole (VRC), a triazole antifungal agent, is a lipophilic drug (LogP 1.65) with low aqueous solubility (0.5 mg/ml in distilled water). It possesses promising characteristics such as broad-spectrum activity, activity against resistant fungal species, good oral bioavailability, and acceptable tolerability. It is highly effective against various fungal isolates associated with keratitis [4, 5].

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