Caspofungin-loaded dissolving microneedles for transcorneal delivery in fungal keratitis

Fungal keratitis is a severe corneal infection that can lead to vision loss and requires prompt, effective antifungal treatment with optimal corneal penetration and minimal toxicity. Conventional treatments, such as natamycin and voriconazole eye drops, face challenges like poor bioavailability, fungal resistance, and epithelial toxicity. In this study, we developed and evaluated dissolvable microneedle (MN) arrays loaded with caspofungin, an inhibitor of β-(1, 3)-D-glucan synthase with a lower resistance compared to azole-based treatments. MNs composed of hyaluronic acid (HA) and polyvinylpyrrolidone (PVP) were fabricated using a micromolding technique. HA provides bioadhesion and hydration, while PVP enhances mechanical strength and solubility. The HA-PVP matrix was designed to ensure the mechanical integrity required for corneal penetration, while allowing rapid dissolution after application. To assess drug delivery, fluorescein isothiocyanate (FITC)-labeled caspofungin was incorporated into the MNs, which facilitated local delivery and distribution throughout the corneal stroma with minimal lateral diffusion. Ex vivo studies using a bovine corneal model demonstrated a five-fold increase in drug delivery compared to conventional eye drops. Antifungal activity of the caspofungin in the MNs was confirmed against Candida albicans, Candida parapsilosis, Candida glabrata, and Aspergillus fumigatus using agar diffusion assays and comparing the zones of inhibition with standard caspofungin solutions. These findings suggest that caspofungin-loaded dissolving MNs represent a promising, minimally invasive approach for overcoming the challenges of ocular drug delivery in fungal keratitis.