Ethosomal drug delivery systems for skin cancer: Mechanistic insights, formulation strategies, and translational challenges.

Introduction: Skin cancer is one of the most prevalent malignancies worldwide, with incidence increasing by approximately 2-3% annually due to prolonged ultraviolet radiation exposure, genetic predisposition, and an ageing population. Conventional treatments, including oral, injectable, and topical therapies, are often limited by poor skin permeability, first-pass metabolism, systemic toxicity, and inadequate tumor targeting. Methods: This review systematically examines ethosomal drug delivery systems, focusing on their composition, mechanism of skin permeation, and formulation strategies. Key aspects such as phospholipid composition, ethanol concentration (20-45% w/w), preparation techniques, and interaction with tumor-altered skin barriers are critically analyzed. Results: Ethosomes, as deformable lipid vesicles, enhance transdermal drug delivery by fluidizing stratum corneum lipid lamellae, enabling deeper dermal penetration. Studies demonstrate improved drug localization, controlled release, and enhanced therapeutic efficacy in various skin cancers, including melanoma, basal cell carcinoma, and squamous cell carcinoma. Applications in chemotherapy, photodynamic therapy, and immunotherapy show promising preclinical outcomes. Conclusion: Despite significant advancements and encouraging preclinical results, challenges such as formulation stability, scalability, regulatory considerations, and long-term safety must be addressed before ethosomal systems can achieve successful clinical translation in skin cancer therapy.