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研究生:戴麗華
研究生(外文):Li-Hua Dai
論文名稱:聚異丙基丙烯醯胺/奈米中空二氧化矽顆粒藥物釋放材料之製備與特性研究
論文名稱(外文):Preparation and characterization of thermosensitive poly(N-isopropylacrylamide) grafted to hollow silica nanoparticles
指導教授:吳宗明吳宗明引用關係
學位類別:碩士
校院名稱:國立中興大學
系所名稱:材料科學與工程學系
學門:工程學門
學類:綜合工程學類
論文種類:學術論文
畢業學年度:96
語文別:中文
論文頁數:121
中文關鍵詞:溫度敏感型生物相容性層接層相轉變溫度藥物載體
外文關鍵詞:thermosensitivebiocompartiblelayer-by-layerlower critical solution temperaturedrug carrier
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  • 被引用被引用:3
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本研究主要目的是製備奈米級中空型且具可溫變功能性之生物相容性藥物載體。實驗是將經過聚電解質改質的聚苯乙烯球,以層接層方式披覆奈米級二氧化矽前驅物,形成PS/SiO2核殼結構奈米複合顆粒,此顆粒再經四氫夫喃侵蝕,而製備出中空二氧化矽殼球。最後將溫度敏感型高分子接枝於複合顆粒表面。
由FTIR、SEM和TEM結果顯示,已成功製備 ~110nm中空SiO2殼球及中空溫度敏感型複合顆粒。從化學分析能譜結果,證實添加1、2和4g NIPAM單體量,顆粒載體表面皆有PNIPAM的存在,且隨著NIPAM單體量增加,接枝於顆粒表面之PNIPAM含量亦增加,同時由電子顯微鏡觀察顆粒粒徑大小,亦可獲得粒徑隨單體添加量增加而增大之結果。
經動態光散射儀和微差掃描熱分析儀結果,顯示添加不同NIPAM單體量對LCST並無明顯的差異,所獲得之LCST約在33~36℃,此溫度範圍接近人體體溫,適合作為藥物載體用。而本研究中,除了探討改變單體添加量,所製備藥物載體材料特性之外,主要將進一步提出其藥物釋放模式。
從模擬藥物吸附與釋放結果,顯示低溫吸附量會大於高溫,而低溫釋放率亦會較高溫增加。然而,實驗中以表面披覆少量PNIPAM之載體顆粒,於低溫獲得最佳釋放率 ~ 86 %,從結果指出,PNIPAM 受溫度變化引發結構型態改變,而使顆粒載體於低溫吸附量大於高溫之結果。且顆粒外層披覆PNIPAM 含量會影響藥物擴散行徑,造成藥物吸附速率之差異,並且在釋放試驗亦是獲得相同結果。由此可知,製備的顆粒載體可經由溫度控制,使藥物按設計劑量與選擇適合的藥物釋放模式,以達到治療某種疾病之目的。
This study is focused on the preparation of hollow silica nanoparticle containing the thermosensitive and biocompartible function used as drug carriers.
The hollow silica nanoparticles have been prepared using layer-by-layer technique to coat the polyelectrolyte on the surface of about 100 nm polystyrene latex and SiO2 precursor was reacted with the polyelectrolyte on the surface of PS latex. The fabricated SiO2 coated PS particle was immersed into THF to remove the PS core and then the thermoresponsive polymer, poly(N-isopropylacrylamide)(PNIPAM) was grafted on the surface of hollow nanoparticle using free radical polymerization.
The morphology and physical properties of the synthesized nanoparticles were analyzed by SEM, TEM, FT-IR, XPS, DLS and DSC. Form the results of FTIR, SEM and TEM images, the ~110 nm hollow SiO2 nanoparticle with thermosensitive PNIPAM was successfully prepared. The presence of PNIPAM on the surface of SiO2 nanoparticle was further identified by XPS analysis. The rate of grafted PNIPAM increases with increasing the content of NIPAM monomer. Both DLS and DSC results show the LCSTs detected at 33~36℃ close to human temperature do not change as the NIPAM dosages increases.
The fabricated nanoparticles with thermosensitive and biocompatible function used as drug carrier was further characteristized their drug release behavior at different temperature. The result show that the drug loading and releasing rate were fast at lower temperature. The maximum releasing rate is about 86% for the specimens containing lower content of PNIPAM. Therefore, the fabricated hollow nanoparticle designed as a novel model for drug carrier can be controlled the on-off releasing rate via changing external temperature.
中文摘要 I
Abstract II
總目錄 III
圖目錄 V
表目錄 VIII
第一章 緒論 1
1-1 前言 1
1-2 研究動機與目的 2
1-3 研究方向 3
第二章 理論基礎與文獻回顧 4
2-1 生醫材料簡介 4
2-1-1 奈米技術在醫學領域的應用 5
2-2 藥物載體 6
2-3 核殼結構奈米顆粒 8
2-3-1 核殼結構奈米顆粒之製備 9
2-3-2 聚電解質和二氧化矽 11
2-3-3 核殼結構奈米顆粒之特性分析 16
2-3-4 中空奈米顆粒之製備 19
2-4 智慧型高分子 21
2-4-1 智慧型高分子及其生醫應用潛力 21
2-4-2 智慧型高分子的種類 22
2-4-3 聚異丙基丙烯醯胺 27
2-5 藥物釋放 34
2-5-1 奈米藥物與藥物傳輸 34
2-5-2 藥物釋放機制 35
2-5-3 溫度敏感性複合顆粒應用於藥物釋放 38
第三章 實驗方法與步驟 43
3-1 實驗材料 43
3-2 實驗儀器 46
3-3 實驗總流程 48
3-4 實驗步驟 49
3-4-1 聚苯乙烯乳膠之製備 49
3-4-2 二氧化矽前驅物之製備 50
3-4-3 聚苯乙烯球表面改質 51
3-4-4 聚苯乙烯/二氧化矽核殼奈米顆粒之製備 52
3-4-5 中空二氧化矽殼球之製備 53
3-4-6 聚異丙基丙烯醯胺接枝中空二氧化矽殼球之製備 54
3-4-7 聚異丙基丙烯醯胺接枝中空二氧化矽殼球之藥物釋放模擬 55
3-4-7-1 藥物吸附試驗 55
3-4-7-2 藥物釋放試驗 56
3-5 實驗樣品代號 57
3-6 材料性質分析 58
3-6-1 傅利葉轉換紅外線光譜儀 58
3-6-2 動態光散射儀 58
3-6-3 場發射掃描式電子顯微鏡 58
3-6-4 分析型電子顯微鏡 58
3-6-5 微差熱掃描熱分析儀 59
3-6-6 原子力掃描顯微鏡 59
3-6-7 紫外光可見光譜儀 59
3-6-8 X射線電子能譜儀 59
第四章 結果與討論 60
4-1 聚苯乙烯奈米顆粒與表面改質 60
4-1-1 聚苯乙烯奈米顆粒之製備與物性分析 60
4-1-2 聚苯乙烯球之表面改質 65
4-2 奈米二氧化矽前驅物之製備與物性分析 68
4-3 聚苯乙烯/二氧化矽核殼奈米顆粒之表面分析與微結構觀察 72
4-4 奈米中空二氧化矽殼球之表面分析與微結構觀察 79
4-5 聚異丙基丙烯醯胺接枝奈米中空二氧化矽殼球複合顆粒之性質 82
4-5-1 PNIPAM接枝中空二氧化矽殼球之表面分析與微結構觀察 82
4-5-2 PNIPAM接枝中空二氧化矽殼球之溫度敏感特性 93
4-5-3 不同NIPAM單體量與複合顆粒之藥物吸附/釋放試驗 97
第五章 結論 112
參考文獻 114
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