Development of two-layer dissolving microneedles loading fluconazole microemulsions for ocular drug delivery

Abstract

Fungal keratitis is a serious issue that can lead to eye problems if not treated properly. Topical fluconazole (FLUZ) is commonly used for treating fungal infections in the eyes, but its limited solubility in water makes it difficult to treat deeper infections. Microemulsions (MEs) and microneedles (MNs) were used to enhance the solubility and bioavailability of FLUZ in order to improve its effectiveness. The study aimed to develop and evaluate the potential of MEs-FLUZ-loaded two-layered dissolving MNs for treating fungal keratitis. The optimal mixture of oil, surfactant, cosurfactant, and water was used to create MEs-FLUZ, which were then loaded into two-layered dissolving MNs. The MNs were evaluated for physical appearance, mechanical properties, penetration ability, dissolution time, in vitro/ex vivo ocular drug delivery, antifungal activity, and stability. The results showed that the MEs-FLUZ-loaded two-layered dissolving MNs effectively treated fungal keratitis with good physical properties, mechanical strength, insertion force, and penetration depth. The MNs formulation completely dissolved in corneal tissue within 3 min and demonstrated a significant permeation profile in MEs-FLUZ-loaded two-layered dissolving MNs higher than others. Furthermore, the antifungal activity of these MNs significantly inhibited fungal growth more than others. The MNs formulations were also found to be stable at 4-25 °C over 6 months. Therefore, the MEs-FLUZ-loaded two-layered dissolving MNs can be a minimally invasive treatment for fungal corneal infection.

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