三團聯聚乙二醇-聚己內酯共聚合物選擇性發酵及降低克林黴素劑量於青春痘治療之研究

Triblock poly(ethylene glycol)-block-poly(ε-caprolactone) for selective fermentation and reduction of dose of clindamycin in the treatment of acne

10.6840/cycu201600855

高馨柔

三團聯 ； 聚乙二醇 ； 發酵 ； 青春痘 ； triblock ； poly(ethylene glycol) ； fermentation ； acne

中原大學生物醫學工程學系學位論文

2016年

碩士

謝明發

繁體中文

表皮葡萄球菌為人體皮膚常見之微生物，能夠發酵甘油、蔗糖以及聚乙二醇類高分子，產生短鏈脂肪酸，且這些發酵產物可以抑制過度生長的青春痘病原菌(痤瘡丙酸桿菌)。本研究從正常人皮膚篩選出黏金色棒狀桿菌，發現該細菌與表皮葡萄球菌均能選擇性地發酵甘油、蔗糖與三團聯聚乙二醇-聚己內酯共聚合物。相反地，痤瘡丙酸桿菌則無法發酵。研究還發現，早期及中期痤瘡患者的痤瘡切片之發炎激素IL-8表現，顯著高於正常皮膚；將該組織與蔗糖、黏金色棒狀桿菌共培養後，能顯著減少IL-8表現。由此推測，痤瘡丙酸桿菌的數量也相對減少。進一步在ICR小鼠耳朵施打痤瘡丙酸桿菌以及三團聯聚乙二醇-聚己內酯共聚合物，發現能夠減少 抗生素克林霉素的使用劑量。因此，透過皮膚篩選出能夠選擇性發酵高分子的黏金色棒狀桿菌，其功效與腸道益生菌類似，可視為一種皮膚益生菌。本研究亦發現三團聯聚乙二醇-聚己內酯共聚合物可作為治療痤瘡丙酸桿菌之佐劑，減少抗生素的使用劑量。

Our results demonstrate that Staphylococcus epidermidis (S. epidermidis) and Corynebacterium aurimucosum (C. aurimucosum), two bacteria in the human skin microbiome, can ferment glycerol, sugars or polyethylene glycol PEG-based polymers to produce various short-chain fatty acids (SCFAs) which suppressed the growth of Propionibacterium acnes (P. acnes), a bacterium highly associated with the progress of acne vulgaris. Sugars and PEG-based polymers were chosen as selective fermentation initiators which exclusively induced the fermentation of S. epidermidis or C. aurimucosum, but not P. acnes. Interestingly, sugars and PEG-based polymers can efficiently suppress the growth of P. acnes. An acne ex vivo explant was established by using acne biopsies collected from patients with acne vulgaris at the early and middle stages. The levels of pro-inflammatory interleukin (IL)-8 cytokine in early- and middle-staged acnes were significantly higher than those in healthy skins. Incubation of acne ex vivo explants with sucrose remarkably reduced the level of IL-8 and the number of P. acnes. Our results demonstrate for the first time that sugars and PEG-based polymers are SFIs which can be used to specifically manipulate the fermentation of probiotic bacteria in the human skin microbiome. Results from mouse studies revealed that PEGDMA and PCL-PEG-PCL, a poly(caprolactone) triblock, function as antibiotic adjuvants which can considerably reduce the effective doses of clindamycin, a clinically-used acne antibiotic. Overall, the novelty of our studies at least includes identifying C. aurimucosum as a skin probiotic bacterium and defining the PEG-based polymers as antibiotic adjuvants.

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