Novel Rifampicin and Indocyanine Green Co-Loaded Perfluorocarbon Nanodroplets Provide Effective In Vivo Photo–Chemo–Probiotic Antimicrobility against Pathogen of Acne Vulgaris Cutibacterium acnes

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.

Bioresponsive Nanoarchitectonics-Integrated Microneedles for Amplified Chemo-Photodynamic Therapy against Acne Vulgaris

“…Acne vulgaris, a chronic inflammatory disease of hair follicles and sebaceous glands, is one of the most prevalent skin disorders that affects up to 80% of adolescents and often persists into adulthood. − The clinical manifestations of acne are comedos, pimples, pustules, nodules, cysts, scars, etc. The pathogenesis of acne can be attributed to many factors, including hyperkeratosis of the pilosebaceous unit, proliferation of Propionibacterium acnes ( P. acnes ), excessive sebaceous gland secretion, inflammation, and also immune response.…”

“…Although various antibiotics and other therapeutic agents have been explored for the treatment of acne (for instance, erythromycin, doxycycline, isotretinoin, benzoyl peroxide, and spironolactone), these conventional drugs are susceptible to inducing drug resistance to P. acnes and detrimental side effects, such as nausea and vomiting, teratogenesis, and skin irritation . Recently, antimicrobial photodynamic therapy (aPDT) has emerged as a highly selective and noninvasive therapeutic modality for overcoming bacteria-related diseases. , The principle of aPDT involves the light-triggered activation of photosensitizers to generate cytotoxic reactive oxygen species (ROS) especially singlet oxygen ( 1 O 2 ), leading to selective oxidative damage to the cellular components (lipids, proteins, and nucleic acids) and thereby bacterial inactivation.…”

The chemical biology of antimicrobial bioactivity derived from kānuka (Kunzea robusta)

“…BPO is more effective when taken as a combination therapy alongside either tretonin or topical antibiotics. However, 1-3% of patients will develop an allergic reaction to this treatment, and other patients will find it unfavourable due to it bleaching the skin (Hsiao et al, 2020).…”

“…However, with the increase in antibiotic resistance of P. acnes, topical antibiotics are rarely given as a monotherapy and more often prescribed in combination with BPO or tretonin (Walsh et al, 2016). Oral antibiotics are also an option for patients that suffer adverse effects to topical treatments; these systemic antibiotics have both antimicrobial and anti-inflammatory properties with the most widely used being tetracycline, doxycycline, minocycline and erythromycin (Hsiao et al, 2020). Current research suggests topical antibiotics have greater efficacy and reduced side effects such as dyspepsia, candidiasis, dental problems and ulceration (Leyden, 2001).…”