- 學位論文
硫酸化軟骨素-丙烯酸甲酯與不同分子量聚乙二醇-二丙烯酸酯雙元水膠在蛋白質藥物之傳遞
Methacrylate Chondroitin Sulfate-Polyethylene Glycol Diacrylate with Different Molecular Weight Dual Hydrogel for Protein Drug Delivery
摘要
硫酸化軟骨素(CS)具有良好生物相容性及生物可分解性，可應用於組織工程或藥物釋放。聚乙二醇(PEG)具有無毒性與良好生物相容性，可應用於藥物治療方面。將上述二化合物修飾成具有雙鍵結構，用以合成共聚物水膠，在藥物包覆設計中，利用物理方式將生物活性分子包入水膠中，探討水膠網狀結構孔洞對於釋放的影響。因此本實驗設計將PEG及CS分別以二丙烯酸酯(acryloyl chloride, DA)和丙烯酸甲酯(methacrylic anhydride, MA)修飾成具備雙鍵的結構，再利用光聚合方式形成水膠，PEG選用分子量為1000、3400、8000、20000 g/mol。之後將形成之水膠利用壓力材料測試機觀察其交聯密度; X光繞射光譜儀(XRD)觀察其結晶情形; 示差掃描熱分析儀(DSC)觀察化合物熔點; 掃描電子顯微鏡(SEM)從微細結構觀察孔洞緻密情形。針對此水膠，於體外模擬體內結腸環境來探討水膠包覆牛血清蛋白(BSA)的控制釋放。由實驗結果可得知，在不同PEG分子量、相同CS-MA 莫耳比例添加形成之水膠，其孔洞、膨潤度、結晶度、藥物釋放會隨PEG分子量增加而增大。在相同PEG分子量、不同CS-MA莫耳比例添加形成之水膠，在物理性質方面較無太大變化。
並列摘要
Chondroitin Sulfate (CS), with a good compatibility and degradable chemical structure, can be used in connective tissues and cartilage. polyethylene glycols (PEG) is non-toxic and well biocompatible, which is useful in medical treatments. In drug-cover design, the copolymer hydrogel that is the compound of the above two chemicals entraps the bioactive moleculars in the gel by physical means, and the network-like structural pores of the hydrogel are used for drug delivery. Therefore, the design of this experiment intends to modify PEG and CS by introducing acryloyl chloride (DA) and methacrylic anhydride (MA) as agents to make the above two copolymers be modified with double bonds, and photopolymerization is applied to creat hydrogels, where the molecular masses of PEG are 1000, 3400, 8000 and 20000 g/mol. Then compression tester is used on the hydrogel created to observe the cross-linking density; X-ray diffraction (XRD) is used to investigate the crystallization; Differential scanning calorimetry (DSC) is used to study the melting point of the hydrogels; and Scanning electron microscope (SEM) is used to examine the density of pore formation and microstructure. For these hydrogels, in vitro simulation is conducted to simulate the environment in a human colon to investigate the use of hydrogel-encapsulated bovine serum albumin (BSA) in control drug release. From the experiment result, it is clear that pore sizes, the degree of swelling, the degree of crystallization and the drug released from the hydrogels increased with the increased of molecular weights of PEG, and yet there is no significant change in the physical characteristics of the hydrogel created with PEG different molecular weights and CS-MA at the same identical molar ratio.