Summary of -Voriconazole–Cyclodextrin Supramolecular Ternary Complex-Loaded Ocular Films for Management of Fungal Keratitis

Document Type

Article

Abstract

Study Background: Fungal keratitis is one of the leading causes of ophthalmic mycosis affecting the vision due to corneal scarring. Voriconazole (VRC) is the most preferred azole antifungal agent for treating ocular mycotic infections. Ocular drug delivery is challenging due to the shorter corneal residence time of the formulation requiring frequent administration, leading to poor patient compliance.

Research Goals and Hypotheses: The present study aimed at improving the solubility, transcorneal permeation, and efficacy of voriconazole via the formation of cyclodextrin-based ternary complexes and incorporation of the complex into mucoadhesive films.

Methodological Approach: A phase solubility study suggested a ∼14-fold improvement in VRC solubility, whereas physicochemical characterization confirmed the inclusion of VRC in the cyclodextrin inner cavity. In silico docking studies were performed to predict the docking conformation and stability of the inclusion complex.

Results and Discoveries: Complex-loaded films showed sustained release of voriconazole from the films and improved transcorneal permeation by ∼4-fold with an improved flux of 8.36 μg/(cm2 h) for ternary complex-loaded films compared to 1.86 μg/(cm2 h) for the pure VRC film. The 3-[4,5-dimethylthiazol- 2-yl]-2,5-diphenyltetrazolium bromide (MTT) and hen’s egg-chorioallantoic membrane test (HET-CAM) assays confirmed that the complexes and ocular films were nonirritant and safe for ocular administration. The antifungal study performed using Aspergillus fumigatus and Fusarium oxysporum suggested improved antifungal activity compared to the pure drug film. In conclusion, the supramolecular cyclodextrin ternary complex proved to be a promising strategy for enhancing the solubility and permeability and augmenting the antifungal activity of voriconazole in the management of fungal keratitis.

Publication Date

2021

Recommended Citation

P. Suvarna, Chaudhari P, S. Birangal, L.S. Mallela, S. Roy, A. Koteshwara, J.M. Aranjani, S.A. Lewis, Voriconazole–Cyclodextrin Supramolecular Ternary ComplexLoaded Ocular Films for Management of Fungal Keratitis, Mol. Pharm. 19 (2021) 258– 273.

Publication Date

2021

Link to Full Text

Share

COinS