Enhanced Transdermal Peptide-Modified Flexible Liposomes for Efficient Percutaneous Delivery of Chrysomycin A to Treat Subcutaneous Melanoma and Intradermal MRSA Infection.

Superficial skin diseases, including skin infections and tumors, are common health care burdens. In this study, we explored the in vivo activity of chrysomycin A (CA) and further constructed a transdermal liposomal CA formulation for the simultaneous treatment of cutaneous melanoma and cutaneous methicillin-resistant Staphylococcus aureus (MRSA) infection. The prepared liposomes (TD-LP-CA) displayed a strong antitumor effect with an IC 50 value of less than 0.1 µM in B16-F10 cells, suppressed the proliferation of MRSA with a minimum inhibitory concentration (MIC) of 1 µM, and eradicated established MRSA biofilms at 10 × MIC in vitro. More importantly, TD-LP-CA showed enhanced stratum corneum (SC) penetration, reaching more than 500 µm beneath the skin's surface due to modification with the TD peptide, and demonstrated excellent subcutaneous tumor penetration after skin application in vivo. TD-LP-CA displayed an excellent therapeutic effect against intradermal MRSA infection in mice after topical dermal administration, as well as a moderate inhibitory effect on subcutaneous melanoma with a 75% tumor inhibition rate. The liposomes prepared herein could be a promising carrier for transcutaneous CA transfer for the treatment of superficial diseases such as skin tumors and infections due to their ability to overcome the skin barrier. This article is protected by copyright. All rights reserved.