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研究生: 張揚狀
Chang, Yang-Chuang
論文名稱: 表面被覆幾丁聚醣之多功能磁性奈米載體 的製備與應用
Preparation and Applications of Chitosan-coated Multifunctional Magnetic Nano-Carrier
指導教授: 陳東煌
Chen, Dong-Hwang
學位類別: 博士
Doctor
系所名稱: 工學院 - 化學工程學系
Department of Chemical Engineering
論文出版年: 2005
畢業學年度: 93
語文別: 中文
論文頁數: 217
中文關鍵詞: 幾丁聚醣奈米磁性
外文關鍵詞: nano, chitosan, magnetic
相關次數: 點閱:70下載:2
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  •   本論文係有關幾丁聚醣被覆之多功能氧化鐵磁性奈米粒子的製備及其作為磁性奈米吸附劑、磁性可操控觸媒載體、與藥物磁性標的載體等方面的應用研究。

      關於幾丁聚醣被覆之氧化鐵磁性奈米粒子的製備,係先將幾丁聚醣進行羧基甲基化反應,再藉由碳二醯胺的活化直接共價鍵結在氧化鐵奈米粒子上。穿透式電子顯微鏡與動態光散射分析儀之分析顯示,幾丁聚醣被覆之磁性奈米粒子具有單分散性,其平均粒徑為13.5 nm,平均水力直徑為17.1 nm。由X射線繞射儀分析得知,磁性奈米粒子為四氧化三鐵之尖晶石結構,且不因幾丁聚醣的被覆而改變。此外,由磁性量測得知,所得磁性奈米粒子具有超順磁性,其飽和磁化量、殘留磁化量、保磁力與squareness分別為63.2 emu/g、0.83 emu/g、8.3 Oe和0.013。而由傅立葉轉換紅外線光譜儀與界面電位分析儀之分析可確認幾丁聚醣以共價鍵結方式被覆在氧化鐵奈米粒子上,其鍵結重量百分比約為4.92wt%,等電點則為5.95。

      關於幾丁聚醣被覆之氧化鐵奈米粒子作為新型磁性奈米吸附劑之研究,主要探討其藉由螯合及/或陰離子交換機制吸附水溶液中之金屬陽離子、金屬鹽類陰離子、和酸性染料的效能。實驗結果顯示,因比表面積大且無孔內擴散阻力,故吸附容量甚高且吸附平衡時間明顯比微米級之吸附劑要來的短。此外,此磁性奈米吸附劑吸附Cu2+、AuCl4-、及酸性染料AO12與AG25皆遵守Langmuir恆溫吸附模式,而動力學分析則顯示,吸附AuCl4-與酸性染料係遵守擬二階動力方程式。因此,以幾丁聚醣被覆之氧化鐵奈米粒子作為磁性奈米吸附劑,不但可以磁性操控,同時擁有高吸附速率與高吸附容量之優點,可有效的應用在分離程序上。

      關於幾丁聚醣被覆之氧化鐵奈米粒子作為新型磁性可操控觸媒載體之研究,首先將銅離子吸附於幾丁聚醣被覆之磁性載體,探討其催化雙硝基苯磷酸酯水解反應之效能。其次,將金離子吸附於幾丁聚醣被覆之磁性載體,並進一步還原成金奈米粒子,探討其催化硝基酚化合物還原反應之效能。實驗結果顯示,吸附或承載於幾丁聚醣被覆之磁性載體的銅離子或金奈米粒子,皆具有良好的觸媒作用,且經由磁性回收與多次反覆使用後,仍可維持高的觸媒活性,顯示此載體具有良好的安定性。因此,幾丁聚醣被覆之氧化鐵奈米粒子確可作為一優良之磁性可操控觸媒載體,應用於觸媒反應程序上。

      關於幾丁聚醣被覆之氧化鐵奈米粒子作為新型藥物磁性標的載體之研究,係將抗癌藥物epirubicin吸附於幾丁聚醣被覆之磁性載體,並評估此複合物對體外抗癌之效率。吸附研究顯示,此複合物在pH 3~7與25~40℃間相當穩定,且高epirubicin負載量可以達成。而以牛血清蛋白溶液與0.03M磷酸緩衝溶液進行epirubicin的脫附,則分別約需150與300分鐘才會達到80%的釋放量。此外,口腔癌細胞毒殺的體外試驗顯示,epirubicin與幾丁聚醣磁性奈米載體所形成之複合物對癌細胞具有與epirubicin單獨存在時相似的毒殺效果。由於幾丁聚醣被覆之磁性奈米載體同時兼具磁性標的、藥物治療與核磁共振顯影的功能,因此在生醫領域上將極有用處。

     This dissertation concerns the preparation of chitosan-coated multifunctional iron oxide magnetic nanoparticles and their uses as the magnetic nano-adsorbent, the magnetically manipulated catalyst carrier, and the magnetic targeting carrier for drugs.

     The chitosan-coated iron oxide nanoparticles were prepared by the carboxymethylation of chitosan and the followed covalently binding on the surface of iron oxide nanoparticles via carbodiimide activation. Transmission electron microscopy (TEM) micrograph and dynamic light scattering (DLS) measurement showed that the chitosan-coated iron oxide nanoparticles were monodisperse with a mean core diameter of 13.5 nm and a mean hydrodynamic diameter of 17.1 nm. X-ray diffraction (XRD) patterns indicated the iron oxide nanoparticles were pure Fe3O4 with a spinel structure, and the binding of chitosan did not result in the phase change. In addition, the magnetic measurement revealed that they were superparamagnetic with a saturation magnetization of 63.2 emu/g, a remanent magnetization of 0.83 emu/g, a coercivity of 8.3 Oe, and a squareness of 0.013. The covalently binding of chitosan onto the surface of iron oxide nanoparticles was demonstrated by FTIR analysis and the measurement of zeta potential. The weight percentage of chitosan bound onto Fe3O4 nanoparticles was about 4.92 wt%, and the isoelectric point of the product was 5.95.

     For the study on the use of the chitosan-coated iron oxide nanoparticles as a novel magnetic nano-adsorbent, its capability for the adsorption of metal cations, metal anions, and acid dyes from the aqueous solutions via chelating and/or anion exchange mechanism was examined. The results showed the adsorption capacity was quite high and the time required to reach the equilibrium was significantly shorter than those for the micro-sized adsorbents due to the high specific surface area and the absence of pore diffusion resistance. Moreover, the adsorption of Cu2+ ions, AuCl4- ions, and acid dyes AO12 and AG25 all obeyed the Langmuir equation, and the adsorption kinetics of AuCl4- ions and acid dyes revealed both the adsorption processes obeyed the pseudo-second-order kinetic model. Thus, the chitosan-coated iron oxide nanoparticles as a magnetic nano-adsorbent not only could be magnetically manipulated but also possessed the advantages of fast adsorption and high adsorption capacity. They are expected to be efficiently applied in separation processes.

     For the study on the use of the chitosan-coated iron oxide nanoparticles as a novel magnetically manipulated catalyst carrier, Cu2+ ions were adsorbed and their ability for the catalytic hydrolysis of bis(4-nitrophenyl) phosphate (BNPP) was examined. In addition, AuCl4- ions were adsorbed and reduced into Au nanoparticles. Their ability for the catalytic reduction of aromatic nitro compounds was investigated. The results showed both the Cu2+ ions and Au nanoparticles, adsorbed and supported chitosan-coated magnetic carriers respectively, exhibited high catalytic activities. Also, high catalytic activities retained after being reused and magnetically recovery several times, revealing the catalyst carrier had high stability. So, the chitosan-coated iron oxide nanoparticles could be used as a good catalyst carrier which could be magnetically manipulated and applied in catalytic reaction processes.

     For the study on the use of the chitosan-coated iron oxide nanoparticles as a novel magnetic targeting carrier for drugs, the anti-cancer drug epirubicin was adsorbed and the in vitro anti-cancer efficacy of the conjugate was evaluated. The adsorption study indicated that the conjugate was stable at pH 3-7 and 25-40˚C and a high epirubicin loading could be achieved. The desorption kinetics showed that about 80% epirubicin released from the chitosan-coated magnetic carrier after 150 and 300 min in serum and 0.03 M phosphate buffer, respectively. In vitro cytotoxicity evaluation revealed that the epirubicin-loaded magnetic conjugate was able to exhibit comparable efficacy as free epirubicin did alone. Because of the combined functions of magnetic targeting、drug therapy, and MRI diagnosis, the chitosan-coated iron oxide nanoparticles will be quite useful in the field of biomedicine.

    中文摘要……………………………………………...…………….. I 英文摘要……………………………………………...…………….. III 誌謝…………………………………………………………………. V 總目錄………………………………………………………………. VI 表目錄………………………………………………...…………….. X 圖目錄………………………………………………...…………….. XII 符號說明……………………………………………...…………….. XVIII 第一章 緒論 1.1 奈米材料與奈米技術………..………………………………… 1 1.1.1前言………………….……………………………………... 1 1.1.2奈米材料的定義…………….……………………………... 2 1.1.3奈米材料的特性………………….………………………... 2 1.1.4奈米材料的製備…………………………………………… 13 1.1.5奈米材料的應用…………………………………………… 14 1.2幾丁聚醣………………...…………………………...…………. 17 1.2.1簡介……………………………..………………………….. 17 1.2.2幾丁聚醣的基本特性……………………..……………….. 19 1.2.3幾丁聚醣的應用………………………..…………….….… 20 1.3奈米複合材料…………………………...……………….……... 25 1.3.1奈米複合材料的定義與分類………………..…………….. 25 1.3.2無機-無機奈米複合材……………………………..….…… 25 1.3.3有機-有機奈米複合材……………………………..…….… 34 1.3.4有機-無機奈米複合材……………………………...……… 34 1.3.5無機-生物分子奈米複合材…………………………..….… 39 1.4研究動機………………………………….……………...……... 41 第二章 基礎原理 43 2.1磁性材料………………………………………...…...…………. 43 2.1.1磁學理論………………………………..………………….. 43 2.1.2磁性載體技術…………………………..………………….. 53 2.2吸附與催化理論…………………………………………...…… 57 2.2.1吸附理論………………………………………..…..……… 57 2.2.2催化理論………………………………………..…..……… 61 第三章 材料與方法 67 3.1藥品………………………………..……………..………….….. 67 3.2儀器………………………………...………………..….………. 70 3.3材料………………………………...…………………..…….…. 71 3.4幾丁聚醣被覆之磁性奈米粒子之製備…………..……………. 72 3.4.1磁性奈米粒子之製備……………………………….....…... 72 3.4.2羧基甲基化幾丁聚醣之製備………………………..…..… 72 3.4.3幾丁聚醣被覆之磁性奈米粒子之製備………………..….. 73 3.4.4幾丁聚醣被覆之磁性奈米粒子之特性分析…………...…. 73 3.5幾丁聚醣被覆之磁性奈米粒子作為吸附劑之應用…............... 79 3.5.1磁性奈米吸附劑之性能鑑定…………………………..….. 79 3.5.2金屬陽離子之吸附………………………………..……….. 79 3.5.3金屬鹽類陰離子之吸附……………………………..…….. 80 3.5.4酸性染料之吸附………………..………..………………… 80 3.6幾丁聚醣被覆之磁性奈米粒子作為觸媒載體之應用…........... 81 3.6.1 螯合銅離子之磁性奈米載體作為磷酸酯化合物之水解觸媒………81 3.6.2結合金奈米粒子之磁性奈米載體作為硝基酚之還原觸媒………… 85 3.7幾丁聚醣被覆之磁性奈米粒子作為藥物標的之應用………... 88 3.7.1抗癌藥物epirubicin在磁性奈米粒子上之吸附研究…….. 88 3.7.2 結合抗癌藥物epirubicin之磁性奈米載體在體外試驗之口腔癌 細胞毒殺研究………………………….………… 88 第四章 結果與討論 90 4.1幾丁聚醣被覆之磁性奈米粒子之製備…..……..……..………. 90 4.1.1粒子型態與粒徑大小……….………………..….………… 90 4.1.2晶相結構與磁性……….…………………………..………. 92 4.1.3合成機制……….…………………………………..………. 95 4.1.4幾丁聚醣鍵結量之估算……………………………..…..… 95 4.1.5界面電位與等電點……………………………………..….. 98 4.2幾丁聚醣被覆之磁性奈米粒子作為吸附劑之研究..…............. 100 4.2.1作為奈米吸附劑之性能鑑定…………………………..….. 100 4.2.2金屬陽離子之吸附……………………………..………….. 102 4.2.3金屬鹽類陰離子之吸附…………………………..……...... 108 4.2.4酸性染料之吸附……………………………………….…... 118 4.3幾丁聚醣被覆之磁性奈米粒子作為觸媒載體之研究..….…… 131 4.3.1螯合銅離子之磁性奈米載體作為磷酸酯化合物之水解觸媒……… 131 4.3.2結合金奈米粒子之磁性奈米載體作為硝基酚之還原觸媒.........144 4.4幾丁聚醣被覆之磁性奈米粒子作為藥物標的之研究………... 158 4.4.1抗癌藥物epirubicin在磁性奈米粒子上之吸附研究…….. 158 4.4.2結合抗癌藥物epirubicin之磁性奈米載體在體外試驗之口腔癌 細胞毒殺研究………………………….………… 160 第五章 結論……………………………………….……..…….…. 168 參考文獻……………………………………………………...…….. 175 自述……………………………………………..……………….….. 215

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