L ipid N anocarriers for T ransdermal A nticancer D rug D elivery

Skin cancer is one of the most common malignant tumors worldwide but its incidence is continuously increasing. The conventional treatment methods are limited by the systemic toxicity, low bioavailability and insufficient targeting. Lipid nanocarriers can encapsulate a wide range of therapeutic agents and may help overcome the stratum corneum barrier, making them promising carriers for transdermal anticancer delivery. This review summarizes recent progress in lipid-based nanocarriers, including Liposomes, Ethosomes, Transfersomes and Transethosomes. The transdermal penetration mechanism, the preparation methods and the applications in delivery chemotherapeutic drugs, natural active ingredient and dual-drug combination therapy for skin cancer are focused on. Overall, the evidence reviewed here suggests that the design parameters of the carriers jointly determine the transdermal efficiency, the dual-drug co-loading strategy can achieve a synergistic anti-cancer effect and avoid multi-drug resistance. The transdermal mechanism is still unclear, and the key problems such as the process scale-up and the long-term safety still need to be tackled. This review provides a systematic framework for the understanding of the structure-activity relationship of the lipid nanocarrier and also gives a practical guidance for the rational design of next-generation transdermal delivery systems, and it is hoped that it can promote the clinical translation of these promising nanomedicines in the treatment of the skin cancer.