Innovative ethosomal nanocarriers for transdermal delivery of antifungal agents: A systematic review of physicochemical advances to overcome drug resistance

Invasive fungal infections remain a major cause of global morbidity and mortality, with resistance to conventional antifungal agents posing an increasing challenge. Ethosomal nanocarriers have gained attention as effective transdermal delivery systems that enhance drug permeation, retention, and therapeutic outcomes. This systematic review assesses the physicochemical properties, formulation approaches, and antifungal performance of ethosomal nanocarriers in transdermal drug delivery. A thorough literature search was performed across PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar, covering publications from 2000 to 2026. Studies were included if they reported ethosomal formulations for antifungal agents with physicochemical characterization and efficacy data. Screening of titles and abstracts was followed by full-text review using predefined eligibility criteria. Key data, including formulation composition, vesicle size, entrapment efficiency, skin permeation, and antifungal activity, were extracted and qualitatively analyzed. Findings consistently showed that ethosomal formulations achieved nanoscale vesicle sizes, high entrapment efficiency, superior skin permeation, and greater antifungal activity relative to conventional formulations. Ethanol-driven vesicular flexibility and lipid interactions with the stratum corneum were central to these improvements. Nevertheless, heterogeneity in formulation composition, evaluation methods, and experimental models hindered direct cross-study comparisons. In conclusion, ethosomal nanocarriers offer a compelling approach to improving transdermal antifungal therapy and addressing drug resistance. Standardized research and rigorous clinical evaluation are still needed before widespread clinical adoption can be realized.