Luliconazole Topical Dermal Drug Delivery for Superficial Fungal Infections: Penetration Hurdles and Role of Functional Nanomaterials

Abstract

Luliconazole is the first and only anti-fungal agent approved for the short-term treatment of superficial fungal infections. However, commercially available conventional topical dermal drug delivery cargo of luliconazole is associated with certain limitations, like lower skin permeation and shorter skin retention of drug. Therefore, the present review is an attempt to unravel the penetration hurdles in luliconazole topical dermal drug delivery. Moreover, we have also summarized the activity of functional nanomaterials-based drug delivery systems employed by the scientific fraternity to improve luliconazole efficacy in superficial fungal infections on a case-to-case basis. In addition, efforts have also been made to unveil the critically acclaimed mechanism of action of luliconazole against fungal cells. Under the framework of future prospects, we have analyzed the combination of luliconazole with isoquercetin using the in-silico docking technique for offering synergistic antifungal activity. Isoquercetin exhibited a good affinity for superoxide dismutase (SOD), a fungal target, owing to the formation of hydrogen bonds with Glu132, Glu133, and Arg143, in addition to a few hydrophobic interactions. On the other hand, luliconazole inhibited lanosterol-14α-demethylase, and consequently blocked ergosterol. In addition, nanotechnology and artificial neural network (ANN) derived integrated drug delivery systems may also be explored for augmenting the luliconazole therapeutic efficacy in topical fungal infections. Synergy of ANN models along with topical nanoscaled drug delivery may help to achieve critical quality attributes (CQA), leading to commercial success of luliconazole.

Keywords: Luliconazole; artificial neural network; drug delivery; in-silico docking; isoquercetin; topical fungal infections.