Stability enhancement of Amphotericin B using 3D printed biomimetic polymeric corneal patch to treat fungal infections.

Amphotericin B eye drops (reconstituted from lyophilized Amphotericin B formulation indicated for intravenous use) is used off-label for fungal keratitis. However, the reconstituted formulation is stable only for a week, even after refrigeration. Moreover, a high dosing frequency makes it an inconvenient treatment practice. The current study aims to develop a stable Amphotericin B-loaded biomimetic polymeric corneal patch (Ampat) using 3D printing. Hydroxypropyl methylcellulose and chitosan were used to formulate Ampat, which was then characterized for its physical and mechanical properties. The stability studies were performed at different conditions, protected from light. Further, the therapeutic efficacy of Ampat was evaluated against Candida albicans-induced fungal keratitis using ex vivo and in vivo efficacy models. Amphotericin B in Ampat was found to be stable at room temperature (25 °C) and refrigerated conditions for at least two months. Computer simulations showed that the hydrolysis was a major degradation mechanism of Amphotericin B and was reduced when loaded in the polymeric corneal patch. The ex vivo and in vivo studies show that Ampat was as efficacious as the marketed Amphotericin B formulation but with a reduced administration frequency (1 vs 12 times per day). The present study demonstrated Ampat as a potential alternative to reconstituted lipid-bound eye drops to treat fungal keratitis.