Advanced Topical Drug Delivery for Cutaneous Candidiasis: SkinTargeted Formulation Strategies, Biofilm-Responsive Systems, and Translational Challenges

Abstract

Cutaneous candidiasis is a clinically important superficial fungal infection predominantly caused by Candida albicans, although non-albicans Candida species are increasingly recognized. Disruption of the skin barrier, moisture, maceration, metabolic disorders, antimicrobial exposure, immunological dysfunction, and altered skin microbiota can promote Candida colonization and infection. Conventional topical antifungal formulations are effective in many localized infections; however, poor drug solubility, limited skin retention, rapid drug removal, repeated application, and variable patient adherence may restrict therapeutic performance. Biofilm formation and emerging antifungal resistance further complicate treatment. Advanced topical drug-delivery systems provide opportunities to improve drug solubility, controlled release, skin localization, and residence time. This review critically discusses liposomes, niosomes, transfersomes, ethosomes, nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, nanogels, and nanocarrier–hydrogel systems for topical antifungal delivery. Particular emphasis is placed on lipid-based nanocarriers, Candida biofilm modulation, skin targeting, and the relationship between drug release, skin permeation, dermal deposition, and therapeutic efficacy. Recent Candida-specific studies demonstrating improved skin retention and antifungal activity are evaluated along with their methodological and translational limitations. The review also addresses quality-by-design approaches, quantitative skin-deposition assessment, biologically relevant evaluation models, safety, scale-up, regulatory considerations, and clinical translation. Importantly, enhanced transdermal permeation should not be considered synonymous with improved topical therapy; for superficial candidiasis, the desired pharmaceutical outcome is sustained antifungal exposure at the infected skin compartment with minimal unnecessary systemic absorption. Finally, a precision topical antifungal framework integrating Candida phenotype, drug properties, carrier selection, skin localization, efficacy, safety, and manufacturability is proposed. Future research should focus on standardized Candida-specific models, biofilm-informed formulation design