Fluconazole-loaded Hyaluronic Acid-modified Transfersomal Hydrogels Containing D-panthenol for Ocular Delivery in Fungal Keratitis Management

Biswarup Das; Amit Kumar Nayak; Subrata Mallick

doi:10.2174/0115672018342369241018050810

Fluconazole-loaded Hyaluronic Acid-modified Transfersomal Hydrogels Containing D-panthenol for Ocular Delivery in Fungal Keratitis Management

Curr Drug Deliv. 2024 Oct 18. doi: 10.2174/0115672018342369241018050810. Online ahead of print.

Authors

Biswarup Das^{1

2}, Amit Kumar Nayak², Subrata Mallick²

Affiliations

¹ Department of Pharmaceutics, Seemanta Institute of Pharmaceutical Sciences, Jharpokharia, Mayurbhanj, 757086, Odisha, India.
² Department of Pharmaceutics, School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, 751003, Odisha, India.

PMID: 39428929
DOI: 10.2174/0115672018342369241018050810

Abstract

Background: Fungal keratitis (mycotic keratitis) is an eye infection in which the cornea is infected by fungi and such fungal keratitis management can be effectively possible by ocular administration of antifungal drugs.

Objective: The main objectives of the present research were to develop and evaluate fluconazoleloaded transfersomal hydrogels for ocular delivery in the effective management of fungal keratitis.

Methods: A 23 factorial design-based approach was used for statistical optimization, where (A) the ratio of lipid to edge activators, (B) the amount of hyaluronic acid (% HA), and (C) the ratio of edge activators (sodium deoxycholate to Span 80) were taken as three factors. The average vesicle diameter (Z, nm) of transfersomes was taken as a response. Further, fluconazole-loaded transfersomes (FTO) were incorporated into 1% Carbopol 940-based hydrogel (OF1) and 2% HMPC K4M-based hydrogel (OF2) containing D-panthenol (5% w/w).

Results: The optimal variable setting for the optimized formulations of FTO was (A) = 9.15, (B) = 0.30%, and (C) = 3.00. FTO exhibited 66.39 nm Z, 0.247 polydispersity index, - 33.10 mV zeta potential, and 65.38 ± 1.77 % DEE, and desirable elasticity. TEM image of FTO demonstrated a unilamellar vesicular structure. The ex vivo ocular permeation of fluconazole from transfersomal hydrogels was sustained over 24 h. All the transfersomal hydrogels showed good bioadhesion and excellent antifungal activity with respect to the zone of inhibition against Candida albicans than Aspergillus fumigates, in vitro. HET-CAM study results demonstrated that both the hydrogels were nonirritant and safe for ocular. Short-term physical stability study suggested the stability of the developed formulation.

Conclusion: The current research demonstrated a new way to enhance the ocular penetration of fluconazole via transfersomal hydrogel formulations for ocular delivery in the effective management of fungal keratitis.

Keywords: Drug delivery; antifungal.; eyes; hydrogels; ophthalmology.