Invasomes for Antifungal Drug Delivery: Structure, Skin Barrier Modulation, Formulation Strategies, and Clinical Translation

Abstract

Fungal infections are a major public health concern globally, particularly in tropical and subtropical regions. High humidity, poor hygiene, and limited access to healthcare facilities increase the risk of fungal infection transmission. Conventional topical antifungal formulations, such as creams, gels, and ointments, have limited efficacy due to poor skin penetration, low bioavailability, rapid clearance from the site of application, and the stratum corneum barrier. These limitations may reduce treatment effectiveness and increase the risk of antifungal resistance. This review systematically summarizes the published literature on invasome-based drug delivery systems, focusing on their structure, composition, preparation methods, physicochemical characterization, and applications in antifungal therapy. Invasomes are novel ultra-deformable lipid vesicles composed of phospholipids, ethanol, and terpenes. These components enhance vesicle flexibility and disrupt the lipid structure of the stratum corneum, thereby significantly increasing drug transdermal permeability. Compared with other vesicular systems, such as liposomes, ethosomes, and transferosomes, invasomes show superior deformability, permeability, and biocompatibility. The performance of invasomes depends mainly on parameters such as particle size, zeta potential, drug entrapment efficiency, and deformability. Invasome formulations containing antifungal agents, such as luliconazole, fluconazole, ketoconazole, clotrimazole, and terbinafine, have demonstrated improved drug delivery and therapeutic outcomes. The high permeability of invasomes is attributed to their synergistic composition, which facilitates penetration into the deeper epidermal and dermal layers. Invasomes can be readily prepared on a large scale and can be incorporated into various topical formulations, making them promising carriers for topical antifungal therapy. However, challenges related to stability, safety, and regulatory approval still need to be addressed. Invasomes represent a promising strategy for improving topical antifungal drug delivery. Their enhanced permeability and drug retention can overcome the limitations of conventional formulations, supporting their potential for effective and targeted treatment of fungal infections.