- 學位論文
PEG/PLGA/PEG水膠高分子的製備與其藥物釋放的研究
Studies of PEG/PLGA/PEG Based Drug Delivery System
摘要
摘要 水膠在製程上，可以避免化學溶劑而使用大量的水，富含水的特性與活體組織相近，因此可應用在低分子量親油性藥物、親水性藥物的藥物傳輸及不穩定生物分子的傳輸如蛋白質、基因、細胞固定與組織工程上。另外水膠在材質上可同時具備生物相容性與生物可分解性，則可進一步應用於體內實驗上。 本研究利用生物可分解材料合成PEG-PLGA-PEG水膠高分子，此水膠在低溫成液狀可包覆親水性藥物，在人體溫度時成凝膠，而其相變化的反應時間快，不會產生burst的現象。在使用時可直接注入至人體，在人體內定型（in situ），可免於外科手術，且藥物釋放後亦不需開刀手術取出，可直接由人體排出。 此種材料稱之為溫度敏感型水膠，文獻上以micelles方式進行相變化形成gel，如商品化的pluronic、tetronics都是類似的材料，其主要是具有疏水性的官能基，如甲基(methyl)、乙基(ethyl) 於分子結構內。利用溫度的不同，造成溶解度的差異形成相變化。 本研究首先利用總體聚合反應合成PEG-PLGA-PEG水膠高分子，並做為藥物傳輸的載體。利用tube reverse 的方式繪製sol-gel 的相變化圖，並包覆親水性藥物萬古黴素（vancomycin），在人體溫度37℃下，觀察其藥物釋放曲線。 另比較在33℃及40℃下親水性藥物萬古黴素（vancomycin）藥物釋放曲線的不同，並利用焦油腦（pyrene）在極性環境下螢光強度會增大的特性，在不同溫度與濃度下，觀察其螢光強度變化並探討其高分子的結構與形成凝膠的原理。
並列摘要
Abstract Hydrogels are capable of containing large amounts of water and resemble nature living tissue so it can be used in drug delivery for low molecular hydrophobic drugs, hydrophilic drugs, peptides, proteins and genes, and can be used as scaffold in tissue engineering. Due to its biocompatibility and biodegradablility, hydrogels could be easily applied in in vivo experiments. This research is to synthesize PEG-PLGA-PEG triblock copolymer with the polyethylene glycol and poly(lactide-co-glycolide). This polymers is gel in body temperature and solution in room temperature. It can be used as an implantable drug delivery system which no any surgical operation is needed after drug depleted. The polymers can also be completely metabolized. These polymers are called temperature-sensitive hydrogels. They are formed by the phase transformation of micelles, the same mechanism as that of pluronics and tetronics. Different temperature makes the solubility change due to the methyl and ethyl functional organic group. PEG-PLGA-PEG triblock copolymer were synthesized by bulk reaction. The characteristics of polymers were validated by H-NMR. Sol-gel phase diagrams were established by the tube reverse method. Vancomycin in vitro release was conducted in 37℃.Comparing the drug delivery curve verse with the different temperature at 32℃ and 40℃, we proposed a gelation mechanism of these copolymer gels.