Development and Optimization of Efinaconazole-Loaded Invasomal Gel for Enhanced Topical Delivery across Keratinized Biological Barriers and Antifungal Efficacy

Abstract

Background: The topical therapy of onychomycosis is problematic because of the highly keratinised nail barrier, impairing medication absorption and thereby reducing therapeutic effectiveness. Efinaconazole is a lipophilic triazole antifungal with low water solubility and limited penetration of keratinised tissues, limiting transungual delivery. The present study aimed to develop and optimize an efinaconazole-loaded invasomal gel to improve topical delivery across a keratinized biological barrier and enhance antifungal performance.

Methods: Invasomes loaded with efinaconazole were produced by thin film hydration process and optimised utilising DoE based methodology. The optimised formulation was included in a Carbopol gel and examined for vesicle features, physicochemical properties, in-vitro drug release, ex-vivo permeability, drug retention and in-vivo antifungal effectiveness in a Trichophyton rubrum-induced Wistar rat model.

Results: The optimised invasomal formulation showed vesicle size of 135 ± 3 nm, polydispersity index of 0.25 ± 0.01 and entrapment efficiency of 91.8 ± 0.7%. The invasomal gel exhibited appropriate pH, viscosity and spreadability for topical purposes. The optimized invasomal gel exhibited an initial rapid-release phase followed by a slower release phase, reaching 91.3 ± 2.5% cumulative release at 12 h and 94.6 ± 1.6% at 24 h.. Ex vivo permeation experiments using excised rat abdominal skin as a surrogate keratinized membrane showed substantially greater drug permeation and skin retention from the optimized invasomal gel than from the conventional gel.

Conclusion: The optimized invasomal gel demonstrated improved physicochemical characteristics, drug permeation, skin retention, and antifungal activity. However, permeation was evaluated using excised rat skin as a surrogate keratinized membrane; therefore, further studies using validated nail permeation models are warranted.