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  1. NTU Theses and Dissertations Repository
  2. 工學院
  3. 醫學工程學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/57718
完整後設資料紀錄
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dc.contributor.advisor黃義侑(Yi-You huang)
dc.contributor.authorYan-Ting Linen
dc.contributor.author林彥廷zh_TW
dc.date.accessioned2021-06-16T06:59:44Z-
dc.date.available2016-07-29
dc.date.copyright2014-07-29
dc.date.issued2014
dc.date.submitted2014-07-16
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27.Jacob, A., R. Wu, M. Zhou, and P. Wang, Mechanism of the Anti-inflammatory Effect of Curcumin: PPAR-gamma Activation. PPAR Res, 2007. 2007.
28.Thangapazham, R.L., A. Puri, S. Tele, R. Blumenthal, and R.K. Maheshwari, Evaluation of a nanotechnology-based carrier for delivery of curcumin in prostate cancer cells. Int J Oncol, 2008. 32(5): p. 1119-1123.
29.Guimaraes, M.R., F.R. Leite, L.C. Spolidorio, K.L. Kirkwood, and C. Rossa, Jr., Curcumin abrogates LPS-induced pro-inflammatory cytokines in RAW 264.7 macrophages. Evidence for novel mechanisms involving SOCS-1, -3 and p38 MAPK. Arch Oral Biol, 2013. 58(10): p. 1309-1317.
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34.Hie, M., M. Yamazaki, and I. Tsukamoto, Curcumin suppresses increased bone resorption by inhibiting osteoclastogenesis in rats with streptozotocin-induced diabetes. Eur J Pharmacol, 2009. 621(1-3): p. 1-9.
35.Anand, P., S.G. Thomas, A.B. Kunnumakkara, C. Sundaram, K.B. Harikumar, B. Sung, S.T. Tharakan, K. Misra, I.K. Priyadarsini, K.N. Rajasekharan, and B.B. Aggarwal, Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. Biochemical Pharmacology, 2008. 76(11): p. 1590-1611.
36.Golub, L.M., H.M. Lee, M.E. Ryan, W.V. Giannobile, J. Payne, and T. Sorsa, Tetracyclines inhibit connective tissue breakdown by multiple non-antimicrobial mechanisms. Adv Dent Res, 1998. 12(2): p. 12-26.
37.Gu, Y., H.M. Lee, N. Napolitano, M. Clemens, Y. Zhang, T. Sorsa, Y. Zhang, F. Johnson, and L.M. Golub, 4-methoxycarbonyl curcumin: a unique inhibitor of both inflammatory mediators and periodontal inflammation. Mediators Inflamm, 2013. 2013.
38.Ionta, F.Q., F.L. Mendonca, G.C. de Oliveira, C.R.B. de Alencar, H.M. Honorio, A.C. Magalhaes, and D. Rios, In vitro assessment of artificial saliva formulations on initial enamel erosion remineralization. Journal of Dentistry, 2014. 42(2): p. 175-179.
39.Amaechi, B.T., S.M. Higham, and W.M. Edgar, Techniques for the production of dental eroded lesions in vitro. J Oral Rehabil, 1999. 26(2): p. 97-102.
40.Lai, P.L., D.W. Hong, T.Y. Lin, L.H. Chen, W.J. Chen, and I.M. Chu, Effect of mixing ceramics with a thermosensitive biodegradable hydrogel as composite graft. Composites Part B: Engineering, 2012. 43(8): p. 3088-3095.
41.Chung, Y.M., K.L. Simmons, A. Gutowska, and B. Jeong, Sol-gel transition temperature of PLGA-g-PEG aqueous solutions. Biomacromolecules, 2002. 3(3): p. 511-516.
42.Kim, M.S., K.S. Seo, H. Hyun, S.K. Kim, G. Khang, and H.B. Lee, Sustained release of bovine serum albumin using implantable wafers prepared by MPEG–PLGA diblock copolymers. International Journal of Pharmaceutics, 2005. 304(1–2): p. 165-177.
43.Das, R.K., N. Kasoju, and U. Bora, Encapsulation of curcumin in alginate-chitosan-pluronic composite nanoparticles for delivery to cancer cells. Nanomedicine: Nanotechnology, Biology and Medicine, 2010. 6(1): p. 153-160.
44.Nair, L.S. and C.T. Laurencin, Biodegradable polymers as biomaterials. Progress in Polymer Science, 2007. 32(8–9): p. 762-798.
45.Letchford, K., A. Sodergard, D. Plackett, S.E. Gilchrist, and H.M. Burt, Lactide and Glycolide Polymers, in Biodegradable Polymers in Clinical Use and Clinical Development. 2011, John Wiley & Sons, Inc. p. 317-365.
46.Kim, J.H., S.C. Gupta, B. Park, V.R. Yadav, and B.B. Aggarwal, Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis. Molecular Nutrition and Food Research, 2012. 56(3): p. 454-465.
47.曹采方、孟煥新、沙月琴、歐陽翔英、李德懿、金力堅、謝昊(編著) (2006)。臨床牙周病學,頁69-82。北京:北京大學醫學出版社。
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/57718-
dc.description.abstract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。zh_TW
dc.description.abstractPeriodontal 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.en
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Previous issue date: 2014
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dc.description.tableofcontents摘要 I
Abstract II
目 錄 IV
圖 目 錄 VII
表 目 錄 IX
第一章、文獻回顧 1
1.1 口腔組織學 1
1.1.1 牙齒 1
1.1.2 牙周組織 2
1.2 牙周病 3
1.2.1 致病機轉 3
1.2.2 牙周病的治療方式 5
1.3 水膠 6
1.3.1 水膠的基本性質 6
1.3.2 水膠的種類 7
1.3.3 水膠的交聯方式 8
1.4 溫度敏感型水膠 9
1.4.1 溫度敏感型水膠的性質 9
1.4.2 溫度敏感型水膠的應用 10
1.5 mPEG-PLGA diblock copolymer 11
1.5.1 材料組成 11
1.5.2 材料性質、優點 12
1.5.3 應用 12
1.6 薑黃素 13
1.6.1 薑黃素基本結構與性質 13
1.6.2 薑黃素之生理活性 14
第二章、實驗動機與目的 16
第三章、實驗器材與方法 18
3.1 實驗藥品 18
3.2 實驗儀器 21
3.3 實驗溶液配製 22
3.4 實驗步驟 25
3.4.1 mPEG-PLGA 溫感型水膠製備 25
3.4.2 核磁共振光譜學 (NMR) 分析 26
3.4.3 膠體滲透層析儀 (GPC) 分析 26
3.4.4 mPEG-PLGA水膠凝膠溫度測定 26
3.4.5 mPEG-PLGA水膠黏度特性分析 27
3.4.6 mPEG-PLGA水膠降解特性測試 27
3.4.7 mPEG-PLGA溫感型水膠控制釋放薑黃素 28
3.4.8 細胞培養 28
3.4.9 細胞毒性測試 29
3.4.10 細胞影像觀察 30
3.4.11 抗發炎能力之評估 30
3.4.12 實驗動物 32
3.4.13 結紮線誘發牙周病 33
3.4.14 齒槽骨高度測量 33
3.4.15 牙周組織病理切片 34
3.4.16 牙周組織發炎因子測量 35
第四章、實驗結果與討論 36
4.1 mPEG-PLGA水膠之化學結構分析 36
4.2 mPEG-PLGA水膠之分子量分析 37
4.3 mPEG-PLGA水膠之 sol-gel-sol 相圖分析 37
4.4 mPEG-PLGA水膠之黏度特性分析 39
4.5 mPEG-PLGA水膠之體外降解行為分析 40
4.6 mPEG-PLGA水膠之藥物釋放分析 42
4.7 mPEG-PLGA水膠之細胞毒性測試 44
4.8 mPEG-PLGA水膠之細胞型態。 46
4.9 mPEG-PLGA水膠之抗發炎能力評估 48
4.10齒槽骨高度測量 51
4.11牙周組織病理切片 54
4.12牙周組織發炎因子測量 56
第五章、結論 58
第六章、參考文獻 59
dc.language.isozh-TW
dc.subject牙周病zh_TW
dc.subject薑黃素zh_TW
dc.subject溫感型水膠zh_TW
dc.subject發炎反應zh_TW
dc.subject齒槽骨溶蝕zh_TW
dc.subjectcurcuminen
dc.subjectalveolar bone resorptionen
dc.subjectperiodontal diseaseen
dc.subjectthermosensitive hydrogelen
dc.subjectinflammationen
dc.title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zh_TW
dc.titleControlled Release of Curcumin from mPEG-PLGA Thermosensitive Hydrogel for Periodontal Tissue Repairen
dc.typeThesis
dc.date.schoolyear102-2
dc.description.degree碩士
dc.contributor.oralexamcommittee鍾次文(Tze-Wen Chung),林森祥(Sen-shang Lin),黃意真(Yi-Cheng Huang)
dc.subject.keyword牙周病,薑黃素,溫感型水膠,發炎反應,齒槽骨溶蝕,zh_TW
dc.subject.keywordperiodontal disease,curcumin,thermosensitive hydrogel,inflammation,alveolar bone resorption,en
dc.relation.page66
dc.rights.note有償授權
dc.date.accepted2014-07-17
dc.contributor.author-college工學院zh_TW
dc.contributor.author-dept醫學工程學研究所zh_TW
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