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標題: 製備纖維素基質交聯水膠及其於親水與疏水性藥物控制釋放之性質
Preparation of Crosslinked Cellulose-based Hydrogels for Controlled Release of Hydrophilic and Hydrophobic Drugs
作者: 何怡昕
Yi-Shin Ho
關鍵字: 水膠;羧甲基纖維素;聚乙二醇;控制釋放;親水性藥物;疏水性藥物;Hydrogel;Carboxymethyl cellulose;Polyethylene glycol;Controlled release;Hydrophilic drug;Hydrophobic drug
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本研究以羧甲基纖維素鈉(Sodium carboxymethyl cellulose;CMCNa)與交聯劑聚乙二醇二縮水甘油醚(Poly(ethylene glycol) diglycidyl ether;PEGDE)製備CMC/PEG 水膠,探討交聯劑分子量及添加量對水膠性質之影響,以 CMC/PEG 包覆親疏水性藥物,不同 pH 值探討其釋放行為及動力學。本研究分為三個部分, 第一部分探討水膠製備條件對於其性質之影響,結果顯示 CMCNa 與 PEGDE 開 環聚合產生醚鍵結構,增加交聯劑 PEGDE 之添加量及分子量,使水膠之熱穩定 性和凝膠分率提高,且平均孔徑和平衡膨潤率降低,結果證實交聯劑使水膠分子 鏈活動性下降、架橋密度與機械性質增加,體外細胞存活率試驗顯示 CMC/PEG 具生物相容性。第二部分為 CMC/PEG 水膠於親水性藥物(Fluorescein sodium salt; FSS)傳輸系統之應用,於不同 pH 值環境下水膠與乾凝膠皆具有緩釋作用,同 時其釋放速率隨交聯劑添加量及分子量增加而下降,其釋放行為符合 Higuchi 動力學模型。第三部分為 CMC/PEG 水膠於疏水性藥物薑黃素(Curcumin;CUR) 傳輸系統之應用,以乳化液提高 CUR 於水相中溶解度達 1600 倍,於不同 pH 值 環境下水膠具有緩釋效果,釋放曲線近零級動力學模型為理想之藥物釋放,研究 結果證實 CMC/PEG 水膠可應用於親疏水性藥物傳輸系統之潛力。

In this study, CMC/PEG hydrogels were synthesized from sodium carboxymethyl cellulose (CMCNa) and poly(ethylene glycol) diglycidyl ether (PEGDE) as a crosslinking agent. The effect of molecular weight and ratio of crosslinking agent on the properties of CMC/PEG hydrogel has been investigated. Hydrophilic and hydrophobic drugs loaded into CMC/PEG hydrogel-based drug delivery systems were monitored the release profiles under in different pH values. This dissertation is divided into three parts, the first part is the synthesis and properties of CMC/PEG hydrogel. The results indicate that CMCNa react with PEGDE to form ether bond by ring opening polymerization. Increasing the molar ratio and molecular weight of PEGDE, the results show that increase of thermal stability and gel fraction and decrease of the average pore diameter and equilibrium swelling ratio of CMC/PEG hydrogel. The results indicate that higher crosslink density and lower molecular chain activity increase and mechanical property. In vitro cytotoxicity indicated CMC/PEG hydrogels have good biocompatibility properties. The second part is the study of CMC/PEG hydrogels and xerogels delivery system for a hydrophilic model drug, fluorescein sodium salt (FSS). CMC/PEG hydrogel and xerogel both show the sustained release profile. The release profiles show the release rate of CMC/PEG delivery system with increasing the molar ratio and molecular weight of PEGDE are retarded. FSS release kinetics of CMC/PEG followed the Higuchi model. The third part is the application of hydrophobic drug delivery system. Emulsification technique increases solubility 1600 times of curcumin (CUR) in water phase. CUR shows sustained release property of CMC/PEG hydrogels in different pH value. The release profile of CUR from CMC/PEG hydrogels followed the ideal zero-order model. Those results demonstrated CMC/PEG hydrogels have great potential as hydrophilic and hydrophobic drug delivery systems.
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