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 healthcare burdens. In this study, the in vivo activity of chrysomycin A (CA) is explored, and a transdermal liposomal CA formulation is further constructed for the simultaneous treatment of cutaneous melanoma and cutaneous methicillin-resistant Staphylococcus aureus (MRSA) infection. The prepared liposomes (TD-LP-CA) display a strong antitumor effect with an IC50 value of less than 0.1 mu m in B16-F10 cells, suppress the proliferation of MRSA with a minimum inhibitory concentration (MIC) of 1 mu m, and eradicate established MRSA biofilms at 10x MIC in vitro. More importantly, TD-LP-CA shows enhanced stratum corneum (SC) penetration, reaching more than 500 mu m beneath the skin's surface due to modification with the TD peptide, and demonstrates excellent subcutaneous tumor penetration after skin application in vivo. TD-LP-CA displays 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 can 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.