Novel Rifampicin and Indocyanine Green Co-Loaded Perfluorocarbon Nanodroplets Provide EffectiveIn VivoPhoto-Chemo-Probiotic Antimicrobility against Pathogen of Acne VulgarisCutibacterium acnes

Acne vulgaris is one of the most prevalent dermatological diseases among adolescents and is often associated with overgrowth ofCutibacterium acnes(C. acnes) in the pilosebaceous units. In this study, we aimed to develop novel rifampicin (RIF) and indocyanine green (ICG) co-loaded perfluorocarbon nanodroplets named RIPNDs which can simultaneously provide photo-, chemo-, and probiotic-antimicrobility, and explore their efficacy in treatment ofC. acnesin vitroandin vivo. The RIPNDs were first characterized as being spherical in shape, with a size of 238.6 +/- 7.51 nm and surface charge of -22.3 +/- 3.5 mV. Then, the optimal dosages ofStaphylococcus epidermidis-produced fermentation product medium (FPM) and RIPND were determined as 25% (v/v) and [RIF]/[ICG] = 3.8/20 mu M, respectively, based on the analyses of inhibition zone and cytotoxicityin vitro. Through thein vivostudy usingC. acnes-inoculated mice, our data showed that the group treated with FPM followed by RIPNDs + near infrared (NIR) irradiation obtained the least granulocytes/macrophage-inflammatory protein 2 expression level in the epidermis, and showed a significantly lower microbial colony population compared to the groups treated with equal amount of RIF, FPM, RIPNDs, and/or combination of the above +/- NIR. These results indicated that the RIPND-mediated photo-chemo-probiotic therapeutics was indeed able to rapidly suppress inflammatory response of the skin and provide a robust antibacterial effect againstC. acneswith limited use of antibiotics. Taken altogether, we anticipate that the RIPND is highly potential for use in the clinical treatment of acne vulgaris.