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  • 學位論文

透明質酸用於藥物載體之研究

The Study of Hyaluronic Acid for Drug Delivery

指導教授 : 王賢達
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摘要


透明質酸(HA)為一種帶負電的天然高分子,大多存在於動物體內較柔軟的結締組織中,以及存在於細胞間質與結締組織之間,具有吸震、潤滑、保護細胞等功能。HA具有良好的生物相容性,在體內可以自然代謝等多項優點,因此常使用HA運用於生物醫學材料與藥物輸送載體。 本實驗利用NaIO4將HA氧化,反應形成氧化透明質酸高分子(OHA),再利用OHA與臨床藥物反應形成氧化透明質酸共軛藥物(OHA-drug)。再利用FTIR、NMR、UV與GPC來分析OHA與OHA-drug的物化性質。此外,利用體外實驗探討OHA-drug的附著性質評估。 結果顯示OHA之氧化程度約為20%,最終產物OHA-drug的接枝率約為5:1 (OHA/drug)。於In vitro研究裡,利用fluoresceinamine來模擬藥物與OHA的反應。再透過IVIS影像系統與螢光顯微鏡觀察。結果顯示,OHA-drug吸附在受傷結腸組織與誘導IBD (Inflammatory bowel disease)結腸組織上之附著效果都比正常結腸組織要來的明顯。綜合以上結果顯示OHA-drug有益於治療炎症性腸病(IBD)。未來研究可檢測OHA-drug之細胞毒性與功效性,以利評估此藥物載體在臨床上的應用。

關鍵字

透明質酸 藥物載體

並列摘要


Hyaluronic acid (HA) is a negatively charged biopolymer, it mostly was found in soft connective tissue and extracellular matrix, and plays an important role in shock absorption, lubrication, and protects cells. HA has good biocompatibility and it was a biodegradable biomaterial, so HA was always to be as biomaterials and drug delivery carrier. In this study, the oxidized HA (OHA) polymer was prepared by oxidative reaction with NaIO4, and then the prepared OHA was reaction with clinical drug to be an OHA-drug. The physicochemical properties of the OHA and OHA-drug have been elucidated by instrumental analysis (FTIR, NMR, UV, and GPC). In additionally, the adhesion efficiency of OHA-drug was evaluated by in vitro study. The result was shown the oxidation degree of OHA is about 20%; and the grafting ratio of finally product (OHA-drug) is 5:1 (OHA / drug). For in vitro study, the fluoresceinamine was simulated for the drug to be reaction with OHA. The OHA-drug has more adhesion efficiency on the injured colon tissue and induced inflammatory bowel disease (IBD) colon tissue than normal colon tissue by IVIS image system and fluorescence microscope. This is very interest to be a therapy for IBD with OHA-drug. In further, OHA-drug will be evaluated with cytotoxicity and function to assess the drug carrier for the clinical application.

並列關鍵字

Hyaluronic acid Drug carrier Oxidized HA

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