Zero order delivery of itraconazole via polymeric micelles incorporated in situ ocular gel for the management of fungal keratitis

• Polymeric micelles loaded in situ gel of itraconazole was developed to overcome poor corneal permeation of commercial eye drop (Itral®).
• The developed formulation showed sustained release (up to 8 h) without irritation.
• Ex vivo transcorneal permeation showed greater permeation than commercial eye drop.
• Histological study indicated safe gel formulation.
• In vitro antifungal activity was greater than Itral®.

The aim of this article is to investigate the role of amphiphilic block copolymer-based polymeric micelles of itraconazole for the management of fungal keratitis to overcome the limitations of the conventional dosage form. The polymeric micelles were made using pluronics above critical micelle concentration. Itraconazole-loaded polymeric micelles prepared by rotary evaporation method were characterized and the optimized micellar formulation (M5) was selected on the basis of least micelle size (79.99 nm), maximum entrapment efficiency (91.32% ± 1.73%) and in vitro permeation (90.28% ± 0.31%) in 8 h, that best fitted zero-order kinetics. M5 was developed as pH sensitive in situ gel and characterized for various parameters. The optimized in situ gel (F5) proved to be superior in its ex vivo transcorneal permeation when compared with Itral® eye drop and pure drug suspension, exhibiting 41.45% ± 0.87% permeation with zero-order kinetics (r2 = 0.994) across goat cornea. Transmission electron microscopy revealed spherical polymeric micelles entrapped in the gel matrix. A spectrum of tests revealed hydration capability, non-irritancy, and histologically safe gel formulation that had appropriate handling characteristics. Conclusively, a controlled release pH-sensitive ocular formulation capable of carrying drug to the anterior segment of the eye via topical delivery was successfully developed for the treatment of fungal keratitis.

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