Abstract
Acne vulgaris is one of the most prevalent dermatological diseases among adolescents and is often associated with overgrowth of Cutibacterium 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 of C. acnes in vitro and in 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 of Staphylococcus epidermidis–produced fermentation product medium (FPM) and RIPND were determined as 25% (v/v) and [RIF]/[ICG] = 3.8/20 μM, respectively, based on the analyses of inhibition zone and cytotoxicity in vitro. Through the in vivo study using C. 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 against C. acnes with limited use of antibiotics. Taken altogether, we anticipate that the RIPND is highly potential for use in the clinical treatment of acne vulgaris.
Highlights
Acne vulgaris (AV) has long been recognized as one of the most common dermatological diseases that affects >80% of adolescents and young adults worldwide [1]
To incorporate the merits of each approach without aforementioned drawbacks, we previously developed a new type of nanometer-sized double-layer perfluorocarbon (PFC) nanocarrier encapsulated with rifampicin (RIF) and indocyanine green (ICG), named rifampicin (RIF)-ICG-loaded PFC nanodroplets (RIPNDs), and preliminarily demonstrated their multi-bactericidal effect, including chemical, photo, and probiotic antimicrobility against C. acnes in vitro [31]
The encapsulation and loading rates provide an inhibitory effect against C. acnes growth, while merely near infrared (NIR) laser irradiation was nontoxic to the bacteria
Summary
Acne vulgaris (AV) has long been recognized as one of the most common dermatological diseases that affects >80% of adolescents and young adults worldwide [1]. This dermatosis is usually associated with microbial colonization of pilosebaceous units with overgrowth of Cutibacterium acnes (C. acnes), a Gram-positive anaerobic commensal microorganism formerly named Propionibacterium acnes, hyperkeratinization, and obstruction of sebaceous follicles as results of abnormal keratinization of the infundibular epithelium and subsequent perifollicular inflammation [2]. Antibiotics without microbial specificity may unselectively destroy all the bacteria and maintain the homeostasis of the microflora at the lesion site. Some of medicines, such as tetracycline, doxycycline, minocycline, and erythromycin, may be able to further suppress the inflammatory response to relieve pain for patients [5]. Long-term or overuse of antibiotics may generate microbial drug resistance and/or induce detrimental side effects, such as pigmental change, atrophy, skin irritation, hepatotoxicity, and/or birth defects [6,7,8,9,10], that highly hinder the utilization of antibiotics in the clinic
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