Design and Fabrication of a Multi-Functional Perfluorocarbon Nanoagent for Simultaneous Photo-Chemo-Biological Antibacterial Therapy of Propionibacterium Acnes

[1] Specific Aim: We aim to design and fabricate multifunctional Indocyanine green (ICG)-Rifampicin (RIF) loaded perfluorocarbon double nanoemulsions (IRPDNEs), and explore their potential for uses in 1) photodynamic-, 2) chemo/antibiotic-, and 3) probiotic antibacterial therapeutics against Propionibacterium acnes (P. acnes)[2] Background: Acne, or commonly known as whelk, is an inflammatory syndrome due to block of hair follicles and is the 8th most common disease in the world. In terms of antibiotic therapy, RIF is one of the most commonly used antimicrobial drugs. However, serious side effects resulted from long-term use or high doses often cause problems for patients. In terms of adjuvant therapeutics of skin disease, phototherapy has been extensively investigated in both academic and clinical aspects since it can provide several advantages such as exceptional bactericidal effect and high availability, and ICG, a water-soluble tricarbocyanine dye, is one of few clinically proved photosensitizers. However, due to its inherent lack of light / thermal stability, the material is greatly limited in practical application. On the other hand, biological antimicrobial therapy conducted by promoting the epidermal probiotics to inhibit pathogens has gained increasing attention in the last decade due to its extremely high biocompatibility. Taken all together, the developed IRPDNEs, a type of photo-chemo-biotic nanoagents, is highly potential for use in acne/P. acne therapy.[3] Advantages: The developed IRPDNE may provide following advantages in clinical use: 1) Since perfluorocarbon possesses relatively high O2-dissolubility, the IRPDNE may carry abundance of oxygen molecules and enhance efficacy of photodynamic therapy accordingly. 2) Both ICG and RIF are encapsulated in the emulsion particles and that may prevent ICG degradation and provide a desired RIF release rate through an appropriate drug carrier design. 3) The IRPDNE can simultaneously provide photo-, chemo-, and biological treatments for P. acne whereby the efficacy of antimicrobial therapy can be dramatically enhanced. 4) Since the IRPDNE can provide adjuvant photo- and probiotic therapies, the dose of RIF provided by the IRPDNE will be lower than that performed in normal antibiotic treatment, and therefore the level of chemotherapy-induced side effect on the patient and drug-resistance of P. acnes can be reduced or abolished accordingly. [4] Research Schedule: The following tasks will be performed orderly in the next three years: 1) Phase I: To fabricate, characterize and optimize the IRPDNE (The 1st Year). 2) Phase II: To assess the antibacterial capability and dose efficacy of the IRPDNE through in vitro microbial assay (The 1st – 2nd Year). 3) Phase III: Animal study and reproducibility verification (The 2nd – 3rd Year).