COMPARATIVE ASSESSMENT OF NAIL PERMEATION, DRUG RETENTION AND ANTIFUNGAL ACTIVITY OF EFINACONAZOLE LOADED INVASOMAL AND CONVENTIONAL GELS FOR TREATMENT OF ONYCHOMYCOSIS

Abstract

Onychomycosis is a widespread fungal infection of the nails that is challenging to treat since the dense keratinised nail plate hinders the penetration of topical antifungal drugs. This study aimed to develop and optimize an efinaconazole loaded invasomal gel and to compare its nail permeation, drug retention and antifungal activity with those of a conventional gel formulation for the treatment of onychomycosis. Invasomal formulations were developed with the use of phospholipid, ethanol and terpene-based components and optimized according to the criteria of vesicle size, entrapment efficiency and polydispersity index. The optimized invasomal gel was characterized in terms of physicochemical properties, in vitro drug release, nail permeation, drug retention and antifungal activity. The optimized invasomal gel formulation had the following characteristics: vesicle size of 135 ± 3 nm, entrapment efficiency of 91.8 ± 0.7% and good physical stability. As compared to the conventional gel, the invasomal gel showed significantly higher values of cumulative drug release, nail permeation, drug retention and antifungal activity. Nail permeation increased twice and drug retention was 122% higher for invasomal gel as compared to the conventional gel. Moreover, invasomal gel caused larger zones of inhibition, low minimum inhibitory concentrations and higher reduction in the fungal burden in the course of in vivo assessment without causing any irritation. The improvement in the performance of invasomal gel is explained by the synergistic action of phospholipids, ethanol and terpenes. This increased the deformability of vesicles, drug transport through the keratinized nail plate and maintained the prolonged drug release from the vesicles. Overall, the optimized efinaconazole-loaded invasomal gel demonstrated significant potential as an advanced topical formulation for improving drug delivery and antifungal efficacy in the management of onychomycosis.