Abstract
Topical application of poorly water-soluble antibiotics cannot achieve the desired therapeutic concentration within cornea. The purpose of this study was to fabricate, characterize and evaluate in-vivo effectiveness of amphotericin B (AmB) containing microneedle ocular patch (MOP) against fungal keratitis. MOP containing free or liposomal AmB was fabricated using micromolding technique to mimic contact lens. MOPs were prepared using dissolvable polymeric matrix including polyvinyl alcohol and polyvinyl pyrrolidone. AmB loaded MOP were studied for their physical and mechanical properties, drug loading and dissolution rate, corneal insertion and drug permeability. MOP loaded with 100 µg AmB had a compression strength of 35.1 ± 6.7 N and required an insertional force of 1.07 ± 0.17 N in excised human cornea. Ex-vivo corneal permeation studies revealed significant enhancement in AmB corneal retention with the application of MOP compared with free AmB or liposomal AmB application. Furthermore, AmB loaded MOP application significantly (P < 0.05) reduced the Candida albicans load within cornea as evaluated in both ex-vivo model and in-vivo rabbit infection model. Histological examination showed that AmB MOP treatment improved the epithelial and stromal differentiation of corneal membrane. AmB containing MOPs can be developed as minimally invasive corneal delivery device for effective treatment of fungal keratitis.
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