Combined photodynamic and antibiotic therapy for skin disorder via lipase-sensitive liposomes with enhanced antimicrobial performance

A lipase-sensitive singlet oxygen-producible and erythromycin-loaded liposome (LSSPL) was developed for combination antibacterial therapy for skin disorder. The LSSPL was synthesized by coating pullulan-pheophorbide a (PU-Pheo A) conjugates onto erythromycin-loaded liposomes composed of 1,2-dipalmitoyl-sn-phosphatidylcholine (DPPC) and cholesterol. Lipase activity was chosen as the environmental-stimulus for the controlled release of erythromycin and Pheo A from LSSPL because skin inflammation-inducing Propionibacterium acnes (P. acnes) secrete extracellular lipases. The presence of P. acnes lipases disrupted LSSPLs by selective cleavage of their ester linkages, liberating erythromycin and Pheo A. Along with the antibacterial effect of erythromycin, additional laser irradiation onto Pheo A further achieved the inhibition of P. acnes growth and treatment of P. acnes-infected inflammation in nude mice back skin. Therefore, antimicrobial therapy, using a stimulus-responsiveness moiety, presents a feasible way to treat bacteria-induced skin disorders.