Solid Lipid Nanoparticles for Topical and Transdermal Delivery of Antifungal Agents: Recent Advances, Challenges, and Future Perspectives

Abstract

The estimated prevalence of fungal infections across the globe is > 1 billion, and it is one of the major causes of morbidity and mortality, especially in immunocompromised patients. Antifungal agents are being delivered through topical and transdermal routes. Conventional formulations using such delivery routes are generally hindered by certain factors including the poor aqueous solubility of antifungal drugs, insufficient skin penetration, rapid drug clearance, and slow drug retention within the tissue, leading to reduced effectiveness of antifungal therapy.  Among different nanocarrier systems that overcome such limitations, solid lipid nanoparticles (SLNs) a type of lipid-based nanocarrier are attracting widespread interest due to their capability of high drug encapsulation efficiency, sustained release, high skin permeation and good drug deposition into infected sites, coupled with the inherent characteristics of being biocompatible and biodegradable lipid matrix, which resemble natural skin lipids thereby ensuring better interaction with stratum corneum and less irritation to the skin. Recent reports highlight the effectiveness of SLN as delivery carrier to improve therapy against a wide spectrum of fungal infections by topical/transdermal administration including fluconazole, terbinafine, clotrimazole, voriconazole and posaconazole; providing a better drug accumulation into the skin, prolonged skin residence time, increased potency and improved frequency reduction for treatment of topical/transdermal fungal infection. The current review provides a concise overview of the epidemiology and pathogenesis of fungal infections, the available antifungal medications, resistance mechanisms of antifungals, recent trends in nanotechnology based drug delivery, and specifically, it is a comprehensive appraisal on formulation strategies, fabrication methodologies, characteristics of SLNs, skin permeation principles, therapeutic potential and translation research on the use of SLNs for transdermal/topical delivery of antifungal drugs, to offer a useful perspective to improve antifungal drug efficacy and a novel safer, effective and user-friendly therapy to treat fungal infections.