Summary of - A supramolecular thermosensitive gel of ketoconazole for ocular applications: In silico, in vitro, and ex vivo studies
Document Type
Article
Abstract
Background: The incidence of corneal fungal infections continues to be a growing concern worldwide. Ocular delivery of antifungal drugs is challenging due to the anatomical and physiological barriers of the eye. The ocular bioavailability of ketoconazole (KTZ), a widely prescribed antifungal agent, is hampered by its limited aqueous solubility and permeation.
Research Goals and Hypotheses: The primary goal of the study was to develop In situ gel to enhance the retention of the drug at the precorneal level, leading to improved permeation and bioavailability of the drug.
Methodological Approach: In the study, the physicochemical properties of KTZ were improved by complexation with sulfobutylether- β-cyclodextrin (SBE-β-CD). KTZ-SBE-β-CD complex was studied in silico with docking and dynamic simulations, followed by wet-lab experiments. The optimized KTZ-SBE-β-CD complex was loaded into a thermosensitive in situ gel to increase corneal bioavailability.
Results and Discoveries: The supramolecular complex increased the solubility of KTZ by 5-fold and exhibited a 10-fold increment in drug release compared to the pure KTZ. Owing to the diffusion, the in situ gel exhibited a more sustained drug release profile. The ex vivo corneal permeation studies showed higher permeation from KTZ-SBE-β-CD in situ gel (flux of ∼19.11 μg/cm2/h) than KTZ in situ gel (flux of ∼1.17 μg/cm2/h). The cytotoxicity assays and the hen's egg chorioallantoic membrane assay (HET-CAM) confirmed the formulations' safety and non-irritancy. In silico-guided design of KTZ-SBE-β-CD inclusion complexes successfully modified the physicochemical properties of KTZ. In addition, the loading of the KTZ-SBE-β-CD complex into an in situ gel significantly increased the precorneal retention and permeation of KTZ, indicating that the developed formulation is a viable modality to treat fungal keratitis.
Publication Date
2022
Recommended Citation
Chaudhari P, R. Naik, L. Sruthi Mallela, S. Roy, S. Birangal, V. Ghate, S. Balladka Kunhanna, S.A. Lewis, A supramolecular thermosensitive gel of ketoconazole for ocular applications: In silico, in vitro, and ex vivo studies, Int. J. Pharm. 613 (2022) 121409.
Publication Date
2022
Recommended Citation
P, Chaudhari; Naik, R.; Sruthi Mallela, L.; Roy, S; Birangal, S.; Ghate, V.; Balladka Kunhanna, S.; and Lewis, S.A., "Summary of - A supramolecular thermosensitive gel of ketoconazole for ocular applications: In silico, in vitro, and ex vivo studies" (2022). Open Access archive. 9265.
https://impressions.manipal.edu/open-access-archive/9265
