Nanosponge-Based Co-Delivery of Clotrimazole and Curcumin for Enhanced Antifungal Therapy: A Comprehensive Review

Abstract

Fungal infections impact more than one billion individuals worldwide and rank among the most common infectious ailments seen in clinical dermatology. Despite the availability of antifungal treatments for many years, treatment failures are still alarmingly frequent due to inadequate drug penetration through the stratum corneum, the creation of drug-resistant biofilms, and the rising occurrence of azole-resistant fungal strains. This review investigates nanosponge technology as a sophisticated drug delivery method that can concurrently tackle these interconnected issues. The study thoroughly analyze the epidemiology and pathophysiology of both superficial and invasive mycoses, examines the pharmacological characteristics and inherent formulation challenges of two complementary antifungal agents—clotrimazole and curcumin—and discusses the structural, synthetic, and functional attributes of cyclodextrin-based nanosponge systems. The mechanistic rationale for integrating these two medications within a cohesive nanosponge platform is thoroughly assessed, including evidence of true pharmacological synergism from checkerboard assays, biofilm inhibition tests, and in vivo studies in murine models. Methods for preparation, such as emulsion solvent diffusion, melt crosslinking, and ultrasound-assisted synthesis, are analyzed along with optimization frameworks based on quality-by-design principles. Significant findings from the literature spanning 2020 to 2025 are summarized, and prospective directions, including stimuli-responsive drug release, fungal-targeting surface modifications, and early-phase clinical assessments, are explored. The gathered evidence positions co-loaded nanosponges of clotrimazole and curcumin as a scientifically strong and clinically promising candidate for advanced topical antifungal treatment.