臺灣博碩士論文加值系統

硫酸化軟骨素(Chondroitin sulfate，CS)為一已知天然多醣體，具有良好的生物相容性（Biocompatibility）和生物可降解性（Biodegradability）。本實驗使用硫酸化軟骨素來製備水膠以作為遞送蛋白質藥物的載體。實驗首先準備三種不同分子量的聚乙二醇二丙烯酸酯（Poly ethylene glycol-diacrylate）和甲基丙烯酸酯基（Methacrylate，MA）接枝率0.28的硫酸化軟骨素-丙烯酸甲酯（Chondroitin sulfate-methacrylatae），並使用這三種不同分子量的PEG-DA且三組CS-MA / PEG-DA比例來製備水膠，共有九種水膠。以此九種水膠進行性質分析，如重量損失測量、膨潤程度測量及壓縮模數測量，並使用掃描式電子顯微鏡（Scanning Electron Microscope，SEM）觀察水膠的表面形態，最後利用這九種水膠包覆牛血清白蛋白（Bovine serum albumin，BSA）來模擬蛋白質藥物的釋放。實驗結果顯示水膠有20~30 %的重量損失。水膠膨潤程度有10~20倍，固定CS-MA / PEG-DA時使用低分子量的PEG1K-DA其膨潤效果要比使用PEG2K-DA 和PEG4K-DA更佳；而固定PEG-DA分子量時則CS-MA / PEG-DA比越高則膨潤效果越佳。壓縮模數G值的高低
與CS-MA / PEG-DA比成正比而與PEG-DA分子量成反比。水膠釋放FITC速率和其膨潤成正比，膨潤效果較佳的低分子量PEG-DA所製成的水膠其釋放也是最為迅速，而分子量較高的PEG-DA製成的水膠相對釋放較緩慢。另外改變不同的CS-MA / PEG-DA比例對於釋放較不顯著。

The goal of this work was to utilize the colon-specifically degradable polymer，chondroitin sulfate (CS)，prepare hydrogel for a protein delivery Polyethylene glycol diacrylate (PEG-DA) with the different molecular masses of PEG (1K, 2K, and 4K g/mol) and methacrylated chondroitin sulfate (CS-MA) with 28 mol% of methacrylated substitution onto chondroitin sulfate were first prepared. Three hydrogels with different ratios between PEG-DA and CS-MA were synthesized and their effects on weight loss, swelling, compression modulus, and controlled release of bovine serum albumin were carried out. We found that about 20 - 30 weight loss were obtained and slightly decreased with the increase in molecular masses of PEG after water extraction of these hydrogels. The swelling percentage all went up with the increase in the contents of CS-MA in hydrogels using three different molecular masses of PEG and especially pronounced in the PEG1K hydrogels. The degree of swelling were within 10-20 times. In an example of PEG-DA with the PEG2K, the compression modulus and effective crosslinking density increased with the ratio increase of CS-MA to PEG-DA. In in vitro drug released studies using FITC-BSA as a model drug. The results showed that the release rates of CS-MA-co-PEGDA hydrogel went hand-in-hand with the swelling data. The high swelling percentages in PEG-DA with lower molecular weight of PEG led to the higher release rate of FITC-BSA. However, the effect of the ratio between CS-MA and PEG-DA on the release rate of FITC-BSA was unpronounced.

圖目錄 IV
表目錄 VII
中文摘要 VIII
英文摘要 X
第一章 緒論 1
1-1 Hydrogel的介紹 1
1-2 水膠之定義 2
1-3 水膠的分類 3
1-4水膠在生醫方面之應用 8
第二章 文獻回顧 10
2-1 硫酸化軟骨素的介紹 10
2-1-1 硫酸化軟骨素之吸收與代謝 15
2-2 聚乙二醇的介紹 17
2-3 牛血清蛋白的介紹 19
2-4 硫酸化軟骨素水膠在聚縮氨酸和蛋白質之研究 20
2-5醣類水膠 23
2-6研究背景與動機 25
第三章 實驗部份 27
3-1 實驗儀器 27
3-2實驗試劑 29
3-3實驗步驟 30
3-3-1 製備CS-MA 單體 30
3-3-2 製備不同分子量的 Poly (ethylene glycol)Diacrylate
(PEG-DA) 32
3-3-3 CS-MA & PEG-DA 雙元水膠的製備 33
3-3-4 雙元水膠之分析 35
A. 重量損失測試 35
B. 雙元水膠之膨潤測試 35
C. 交聯密度測試 36
D. 水膠形成表面及孔洞型態觀察 38
3-3-5 Model drug FITC-BSA 的釋放 39
A. FITC-BSA 的合成 39
B. FITC-BSA檢量線的製作 39
C. 利用雙元水膠包覆FITC-BSA 39
D. FITC-BSA模擬釋放 40
第四章 結果與討論 41
4-1製備Chondroitin Sulfate Methacrylate（CS-MA） 41
4-2製備不同分子量的 Poly (ethylene glycol) Diacrylate（PEG-DA）
43
4-3 CSMA-co-PEGDA共聚物水膠的重量損失測試 47
4-4 CSMA-co-PEGDA共聚物水膠的膨潤程度 48
4-5 CSMA-co-PEGDA共聚物水膠的交聯密度計算 52
4-6水膠包覆FITC-BSA的模擬釋放 56
4-7 水膠型態觀察 62
第五章 結論 64
附錄 66
文獻參考 67

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