Lipase-Sensitive Transfersomes Based on Photosensitizer/Polymerizable Lipid Conjugate for Selective Antimicrobial Photodynamic Therapy of Acne

Acne vulgaris is a common skin problem affecting nearly 90% of adolescents and its development is associated with a colonization of Propionibacterium acnes (P. acnes). Although antibiotics have commonly been used to treat acne, antibiotic resistance of P. acnes is an emerging issue to be solved. In this study, a new way of photodynamic acne therapy is developed using P. acnes lipase-sensitive transfersome (DSPE-PEG-Pheo A (DPP) transfersome). For enhanced selectivity and skin penetration efficiency, DPP transfersomes are prepared from 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000], pheophorbide A (Pheo A), cholesterol, and Tween-80. Incorporation of Tween-80 as an edge activator increases the deformability of DPP transfersomes, enhancing skin penetration efficiency to four times that of free Pheo A. The photoactivity of Pheo A quenched by DPP transfersomes is gradually recovered by selective cleavage of the ester linkage in DPP transfersomes by P. acnes lipases. In vitro P. acnes-specific photoactivity and subsequent selective antimicrobial effect exhibit a greater than 99% loss of P. acnes viability. In vivo antiacne therapeutic effect is confirmed by reduction of swelling volume and thickness of P. acnes-induced nude mice skin. These results demonstrate that DPP transfersome-mediated photodynamic therapy can be used as an alternative method to treat bacterial skin infections.