| 摘要: | [1]研究計畫目的：本計畫目地為針對青春痘/痤瘡丙酸桿菌(Propionibacterium acnes)研製開發結合近紅外光敏劑靛氰綠(Indocyanine green；ICG)與利福黴素(Rifampicin；RIF)之全氟碳奈米乳劑(ICG-RIF-Loaded Perfluorocarbon Double Nano-Emulsion; IRPDNE)，並探索其在1)光動力，2)抗生素以及3)生物性抑菌治療上的效能與應用性。[2]研究計畫背景/緣起：痤瘡，或俗稱之青春痘，是一種由於毛囊阻塞而發炎的反應，是全球第八大常見疾病。在抗生素治療方面，RIF為一專門抗微生物的藥物之一。然而，長期使用或高劑量下嚴重的副作用常為病人帶來困擾。而在皮膚臨床輔助療法中，光治療由於能提供多項優勢，例如優良的殺菌效果與高通用性(不受限於細菌種類)，目前已廣泛地研究於學術及臨床上。其中ICG是目前少數已獲得臨床認證可用於人體的光敏劑。然而，由於其本身不足的光/熱穩定性，使得該物質在實際應用上受到極大的限制。另外，以促進表皮益生菌以抑制致病菌的生物抑菌療法由於其極高的生物可利用性，近年來獲得越來越多的關注。綜合以上，研製開發一多功能及高效能的奈米光-化-生物製劑預期對於青春痘的治療具有高度的臨床價值。[3]研究方法與特點：所製作出的IRPDNE預期有以下特點：1)全氟碳化物具備高度攜帶氧氣的能力，由此IRPDNE可大量提供光動力所需之氧氣分子而因此提升光動力的療效；2) ICG及RIF分子可同時獲得載體保護，如此可改善ICG易受光/熱影響而降解之缺點並提供適切的RIF釋放效果；3)粒子可同時提供物理(光治療)，化學(抗生素治療)以及生物(益生菌療法)等三種消滅細菌的方式，因此徹底治療的成效預期能獲得顯著的提升；4)在光及生物治療的配合下，抗生素(RIF)的有效劑量可望降低，如此得以減輕病人受化學品副作用的影響以及痤瘡丙酸桿菌抗藥性程度。[4]預期完成研究工作項目：未來三年規劃進行之研究工作項目如下：第一階段：完成IRPDNE的製備，性質與功能性檢測以及產品最佳化(第1年)；第二階段：以體外細菌模型評估IRPDNE的抗菌效果(第1-2年)；第三階段：小老鼠試驗與再現性測試(第2-3年)。 ;[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). |
