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    標題: 新陽離子型酸酐-酯共聚合物之合成及生化性質研究
    Synthesis and biological properties of novel cationic poly(anhydride-co-ester)
    作者: 洪維志
    Wei-Chih Hung
    貢獻者: 蕭明達
    嘉南藥理科技大學:生物科技研究所
    關鍵字: 陽離子型高分子
    生物降解性
    基因載體
    聚酸酐
    血液相容性
    blood-compatibility
    Polyanhydride
    gene delivery
    biodegradable
    cationic polymer
    cellular toxicities
    日期: 2006
    上傳時間: 2008-11-24 17:01:53 (UTC+8)
    摘要: 近年來水解性高分子材料已逐漸成為各界矚目的焦點,尤其在生醫材料的使用上,可增加對生物體的生物相容性及生物可降解性,因此可大幅的降低對生物體的細胞毒性。因此在此論文中,我們合成出一個新型的水解性陽離子型高分子:(酸酐-酯)共聚合物(Pea-PA),利用主鏈上帶有胺基的雙酸(AMEDA)加入過量的醋酸氯,熔融聚合後形成主鏈上帶有四級銨的Pea-PA。再以NMR、FT-IR和GPC來鑑定其結構與分子量。隨後,我們對Pea-PA做了一系列的生化試驗,我們從水解及細胞毒性試驗的結果可得知,由於Pea-PA具有自我水解特性,因此不會對細胞產生毒性及負擔,且都遠遠低於目前市售的陽離子型高分子(PEI)。也不會刺激巨噬細胞而產生大量的NO。我們也針對此材料做了一系列的凝血與溶血試驗,提供了一系列的血液相容性的參數,證實了此材料的生物相容性與生物可降解性。在基因載體的運用上,雖然因Pea-PA所攜帶的正電荷不足而無法獨自與DNA達到複合的作用,但我們仍可利用摻合的技術來改善這方面的缺陷且增加複合物的緩衝能力。目前我們開發了這一系列新型的水解性材料以及此材料的一些特性,目的是提供給對水解性陽離子有興趣的學著們有更多的參考材料。
    Water-degradable polymeric materials has already become the focus in recent years. It has been described for various technical and biomedical applications because of the biocompatibility and biodegradable. In this study, a novel cationic polymer, poly(anhydride-co-ester) (Pea-PA) containing quarternary amine groups in the backbone, was synthesized through the reaction between dicarboxylic acid (AMEDA) with amino groups in the backbone and excess acetyl chloride. The structure of Pea-PA was characterized by nuclear magnetic resonance (NMR), Fourier transform infrared (FT-IR) and gel permeation chromatography analysis (GPC). To evaluate their biological properties, we executed a series of experiments. The results revealed that Pea-PA can provide better cytotoxicity profiles than presently used polycation (PEI) due to the biodegradable and biocompatibility. It also can’t induce macrophages to produce abundant NO. Another important aspect of the biomaterial screening refers to their blood-compatibility behaviour and we provided some blood clotting and haemolysis ratio parameters of Pea-PA. Although Pea-PA was not enough positive charge to complex with DNA in the application of gene delivery. But we can use the blending technique to modify the defects and increase the buffering capacity of complex. The novel material (Pea-PA) would be expected low cytotoxicity because of their biodegradable and versatility in terms of chemical and physical properties and an interesting candidate for biomedical applications.
    關聯: 校內校外均不公開
    顯示於類別:[生物科技系(所)] 博碩士論文

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