- 學位論文
以單甲氧基聚乙二醇/聚乳酸甘醇酸溫感型水膠控制釋放薑黃素於牙周組織修復之探討
Controlled Release of Curcumin from mPEG-PLGA Thermosensitive Hydrogel for Periodontal Tissue Repair
摘要
牙周病是一種由牙周病原菌引起的慢性發炎疾病，會對牙周組織如牙齦、牙周韌帶、齒槽骨等進行破壞。牙周病的治療方式是將牙菌斑及牙結石等致病因素去除後，於牙周囊袋內給予四環素類抗生素－鹽酸美諾四環素來進行藥物治療。但鹽酸美諾四環素並非對所有菌株都有效果，且過度使用會導致抗藥菌株的出現。許多研究指出，薑黃素具有抗發炎、抑制蝕骨細胞新生以及抑制基質金屬蛋白酶等多種功效，因此本研究假設其有治療牙周病的效果。但由於薑黃素的水溶性不佳，導致其生物利用率低，因此在本研究中將會利用mPEG-PLGA溫感型水膠作為藥物載體包覆薑黃素，探討其對牙周組織修復的能力。實驗結果顯示，mPEG-PLGA水膠可於37℃下凝膠，在包覆薑黃素後能達到持續釋放的效果，且在37℃下放置4週後仍保有50%的重量。在體外細胞實驗部分，以大鼠牙齦纖維母細胞rGF、人類骨肉瘤細胞株MG-63以及小鼠巨噬細胞株RAW 264.7進行細胞毒性測試，mPEG-PLGA水膠及薑黃素/mPEG-PLGA水膠的細胞存活率均在90%以上，顯示材料具有良好的生物相容性。而抗發炎部分，在Escherichia coli O55:B5的脂多醣誘導下，薑黃素/mPEG-PLGA水膠能有效降低RAW 264.7分泌的發炎因子如IL-1β、IL-6以及TNF-α的表現量。在動物實驗部分，以結紮線誘導Wistar大鼠產生牙周病的動物模式中可以看到，薑黃素/mPEG-PLGA水膠不但可以減少齒槽骨的溶蝕並且能降低牙周組織的發炎程度，顯示薑黃素/mPEG-PLGA水膠在牙周病的治療上具有發展潛力。
並列摘要
Periodontal disease is a chronic inflammatory disease and is caused by periodontal pathogens which destroy the periodontium including the gingival, periodontal ligament and alveolar bone. The treatment of periodontal disease is first to remove the plaque and dental calculus and then minocycline, a tetracycline antibiotics, is administered to the periodontal pocket for pharmacotherapy. However, the minocycline is not always effective on all pathogens, and abusing the antibiotics lead to the creation of resistant strains. Previous studies have reported that curcumin has a variety of biological activities, such as anti-inflammation properties, inhibition of osteoclastogenesis and matrix metalloproteinases. It seems that curcumin has a potential therapeutic role on the periodontal disease. Due to its extremely low solubility and poor stability lead to poor oral bioavailability. In this study, mPEG-PLGA thermosensitive hydrogel was used as a drug carrier of curcumin, and subjected the evaluation on periodontal tissue repair. The results suggest that curcumin-loaded mPEG-PLGA hydrogel has sol-gel transition property at 37℃, and curcumin can be sustainedly released from mPEG-PLGA hydrogel. In degradation test, mPEG-PLGA hydrogel retained 50% of its original weight at 37oC after four weeks. According to in vitro studies, both curcumin-loaded mPEG-PLGA hydrogel and mPEG-PLGA hydrogel have no cytotoxicity on rat gingival fibroblast cell (rGF), human osteosarcoma cell line (MG-63) and Mouse leukaemic monocyte macrophage cell line (RAW 264.7). In addition, curcumin-loaded mPEG-PLGA hydrogel can significantly decrease the expression of inflammatory factors such as IL-1β, IL-6 and TNF-α from RAW 264.7. In vivo studies show that curcumin-loaded mPEG-PLGA hydrogel can reduce the extent of alveolar bone resorption and decreases the inflammatory infiltrate in the gingival tissue. These outcomes suggest that curcumin-loaded mPEG-PLGA hydrogel has a potential therapeutic role on the periodontal disease.