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研究生:蔡佳惠
論文名稱:磁場遙控微球及微膠囊藥物釋放之研究
論文名稱(外文):Magnetic-remote controlled drug release from microsphere and microcapsule
指導教授:陳三元陳三元引用關係
學位類別:碩士
校院名稱:國立交通大學
系所名稱:材料科學與工程系所
學門:工程學門
學類:材料工程學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:中文
論文頁數:123
中文關鍵詞:高分子氧化鐵藥物載體藥物釋放
外文關鍵詞:pHEMAiron oxidesensitive carrierdrug release
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本論文利用氧化鐵奈米粒子備製磁敏感性微球及微膠囊,以發展出新一代智慧型藥物載體,此藥物載體可利用磁場調控藥物釋放,可增加藥物釋放的精準性與應用性。實驗首先利用氧化鐵奈米粒子及HEMA單體混摻後形成磁敏感性pHEMA球體(Microsphere),由IR及電子顯微鏡結果分析發現氧化鐵可與HEMA單體形成部分鍵結而確實包覆於pHEMA球體中,而由XRD、SQUID結果分析確認包覆於pHEMA球體中的氧化鐵結構及磁性質。由於氧化鐵粒子的加入會阻礙HEMA單體間的鍵結聚合情形,因此調控氧化鐵的加入量即可調控pHEMA球體的交鏈程度,實驗發現氧化鐵加入量越多導致pHEMA球體的交鏈聚合程度降低,使得pHEMA球體結構變得鬆散,導致藥物釋放速率增快。pHEMA球體中的氧化鐵粒子在磁場下會受到磁場作用產生Brown及Neel運動導致分子鏈的鬆動,使得藥物隨著分子鏈擾動而向外擴散,因此當磁敏感性pHEMA球體處於AC磁場環境下,pHEMA球體的藥物釋放速率隨著氧化鐵包覆量的增加及磁場強度的增大而增快。
爲了增加藥物的包覆量及解決氧化鐵對藥物的影響,實驗進一步備製磁敏感性微膠囊(Microcapsule)作為藥物釋放載體。實驗中利用不同電性的聚電解質PAH及氧化鐵奈米粒子以靜電力吸引方式吸附於載藥的無機球核上形成聚電解質球殼,當無機球核洗去後即形成中空載藥磁敏感性聚電解質膠囊。實驗中利用SEM、SQUID分析確認磁敏感性聚電解質膠囊結構及磁性質,由於聚電解質材料可受磁場刺激而產生結構變化,因此利用磁場可遙控其藥物釋放量,當氧化鐵在磁場下翻轉運動聚電解質膠囊結構會逐漸鬆散,結構鬆散崩塌進而導致藥物釋放量的增加。此外,在生物結果分析發現聚電解質膠囊與肺癌細胞共同培養12小時後,細胞仍有繁殖現象發生且細胞可將微量膠囊吞噬進入細胞體內,顯示聚電解質膠囊的低毒性及高生物相容性。由此顯現本論文研究之磁敏感性微球及微膠囊皆可以磁場調控其藥物釋放行為,同時微球及微膠囊材料皆具有生物相容性,是良好的生物用藥物釋放載體。
中文摘要 I
Abstract III
目錄 VII
圖目錄 XII
表目錄 XVI
第一章 緒論 1
1.1前言 1
1.2實驗動機 3
第二章 基礎理論與文獻回顧 5
2.1奈米磁性物質 5
2.1.1奈米磁性物質的介紹 5
2.1.1.1磁性物質粒徑尺寸與磁區結構的關係 6
2.1.1.2奈米磁性物質的磁性質 8
2.1.2氧化鐵 10
2.1.3奈米磁性物質在生醫材料上的應用 12
2.1.3.1磁性分離純化(Magnetic separation) 13
2.1.3.2藥物釋放(Drug delivery) 14
2.1.3.3熱療法(Hyperthermia) 16
2.1.3.4核磁共振造影(Magnetic resonance imaging) 18
2.2藥物釋放載體 19
2.2.1 水膠 19
2.2.1.1水膠的介紹及性質 19
2.2.1.2水膠網狀結構的物理特徵 21
2.2.2 層接式自組裝聚電解質 24
2.2.2.1聚電解質 24
2.2.2.2層接式自組裝技術 26
2.2.3 功能性敏感型水膠及聚電解質 30
2.2.3.1pH值敏感型水膠及聚電解質 31
2.2.3.2溫度敏感型水膠及聚電解質 33
2.2.3.3光敏感型水膠及聚電解質 36
2.2.3.4磁敏感型水膠及聚電解質 37
第三章 實驗方法 38
3.1實驗藥品 38
3.2實驗設備及儀器 40
3.3實驗步驟與方法 41
3.3.1磁敏感性水膠球體的製備 43
3.3.2磁敏感性聚電解質球體的製備 45
3.3.3藥物釋放實驗 47
3.3.4細胞培養實驗 48
3.4實驗分析儀器 48
3.4.1掃描式電子顯微鏡(SEM) 48
3.4.2穿透式電子顯微鏡(TEM) 48
3.4.3 X光繞射分析儀(XRD) 49
3.4.4紅外光譜儀(IR) 49
3.4.5熱重分析儀(TGA) 49
3.4.6超導量子干涉儀(SQUID) 50
3.4.7紫外-可見光光譜儀(UV-Vis spectrophotometer) 50
3.4.8螢光光譜儀(Fluorescence Spectrophotometer) 50
3.4.9共軛焦雷射掃描顯微鏡(CLSM) 51
第四章 磁敏感性水膠球體交鏈密度及外加磁場強度對藥物釋放的影
響 52
4.1磁敏感性水膠球體的基本特性分析 52
4.1.1實驗製程與形貌分析 52
4.1.2固定化結構分析 57
4.1.3熱裂解與磁性特性 60
4.2磁敏感性水膠球體交鏈密度對藥物釋放的影響 63
4.3外加磁場對藥物釋放的影響 69
4.3.1外加磁場的ON-OFF效應對藥物釋放的影響 69
4.3.2氧化鐵包覆量在連續性外加磁場下對藥物釋放的影響73
4.3.3不同外加磁場強度對藥物釋放的影響 82
第五章 磁場刺激下磁敏感性聚電解質膠囊對藥物釋放的影響 87
5.1磁敏感性聚電解質膠囊的基本特性分析 87
5.1.1實驗製程與形貌分析 87
5.1.2熱裂解與磁性特性 94
5.2磁場刺激下磁敏感性聚電解質膠囊對藥物釋放的影響 97
5.3聚電解質膠囊的細胞培養情形 103
第六章 結論 107
參考文獻 110
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