Minimally invasive treatment of fungal keratitis with voriconazole microneedle corneal patch.

Fungal keratitis, a disease caused by fungal infection of the cornea, is an eye disease with a high rate of blindness. Despite voriconazole (VCZ) has a good therapeutic effect in the treatment of fungal infection, the use of VCZ in the eye is limited due to the poor solubility of VCZ and the special physiological structure of the eye. In this study, a soluble microneedle (MN) containing VCZ micelles was designed for the eye to effectively deliver VCZ for the treatment of fungal keratitis. The water-insoluble VCZ was first encapsulated into the micelle prepared by polyethylene glycol-15-hydroxystearate (HS-15), and then mixed with hyaluronic acid (HA) and polyvinylpyrrolidone K30 (PVP K30) to create the microneedle patches loaded with voriconazole micelles (VCZ-MN) using a simple mold molding method. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) analysis showed that VCZ was amorphous dispersed in the MN patch. According to in vitro drug release studies, MN patches can consistently release drugs within 6 h. Following the in vivo application of MN, the retention time in the eye is extended to more than 3 h and has good eye biocompatibility. In addition, MN can reversibly penetrate the corneal epithelium and recover within 24 h. The results of in vitro antibacterial study showed that VCZ-MN had good antibacterial activity. The results of eye tissue distribution showed that maximum concentration (Cmax) and area under the concentration-time curve from time zero to infinity (AUC0-∞) in cornea and aqueous humor in MN group were significantly higher than those in eye drops group. The results indicated that VCZ-MN could significantly increase the concentration of VCZ in eye tissue and eye bioavailability. Therefore, VCZ-MN as a minimally invasive drug delivery device, can be used as a safe and effective way to treat fungal keratitis.