臺灣博碩士論文加值系統

本研究主要合成200nm與600nm兩種粒徑的聚苯乙烯球做為模板，利用層接層法將二氧化矽奈米顆粒披覆於聚苯乙烯球上形成聚苯乙烯-二氧化矽核殼結構，再以THF蝕刻移除聚苯乙烯球核心，製備出200nm與600nm的二氧化矽中空球，球體表面再接枝溫度敏感性的高分子PNIPAM，得到具有溫度敏感特性的中空顆粒作為藥物載體。
聚苯乙烯-二氧化矽核殼顆粒，二氧化矽中空球和溫感應答型中空顆粒是以SEM, TEM, FT-IR, DSC, DLS和XPS進行特性分析及研究。溫感應答型中空顆粒的低臨界溶液溫度(Lower critical solution temperature) (LCST)經DSC測量為32~34°C，接近人體體溫，可作為藥物載體應用於藥物釋放。
以FITC作為模擬藥物對溫感應答型中空顆粒進行藥物吸附與釋放試驗，藉由FITC的釋放行為表現以及TEM的觀察結果指出，200nm與600nm溫感應答型中空顆粒的殼層厚度分別為13nm和35nm，經過48小時的藥物釋放後，在25°C下的釋放率分別為86%與54%，在40°C下的釋放率為57%與37%。將上述200nm與600nm溫感應答型中空顆粒的外層二氧化矽披覆次數增加兩次，則殼層厚度分別增加至26nm與52nm，經過48小時的藥物釋放後，在25°C下的釋放率為80%與51%，由藥物釋放的結果顯示，溫感應答型中空顆粒的尺寸造成表面積的不同，因此小尺寸的藥物載體具有較高的藥物釋放率，而溫度的改變影響了溫感應答型中空顆粒表面PNIPAM分子鏈段的狀態，因此在低溫的藥物釋放率大於高溫，隨著溫感應答型中空顆粒的二氧化矽披覆次數增加，原有的孔洞被二氧化矽奈米顆粒所覆蓋，造成藥物釋放率的下降，由以上結果可知，利用溫度的控制或是設計不同尺寸與殼層厚度的溫感應答型中空顆粒可調整藥物的釋放行為以因應特定疾病的治療需要。

In this study, the hollow SiO2 particles coated by thermosensitive poly(N–isopropylacrylamide–co–3-trimethoxysilylpropylmethacrylate)(PNIPAM) have been fabricated through Layer-by-layer technique and radical polymerization. The 200nm and 600nm hollow SiO2 particles were first synthesized using 200nm and 600nm polystyrene(PS) particles served as a core and then coated by 13nm SiO2 nanoparticles using Layer-by-layer method. The PS particles were removed by tetrahydrofuran(THF) at 60°C to obtain hollow SiO2 particle. The hollow SiO2 particles were then coated by PNIPAM using radical polymerization to form the thermosensitive and hollow SiO2 particles. The characteristic and drug loading / release behavior of thermosensitive and hollow SiO2 particles were investigated using SEM, TEM, FT-IR, DSC, DLS and XPS.
The DSC data indicated the Lower critical solution temperature (LCST) of thermosensitive and hollow SiO2 particles is in the range of 32~34°C, which is close to human temperature. These results reveal that the fabricated particles can be used as drug carrier.
The poduced thermosensitive silica hollow sphere were applied to study the effectes of the shell thickness on the release efficiency for (flourescein isothiocyanate，FITC). The shell thickness of thermosensitive silica hollow sphere in 200 nm and 600 nm diameter was 13 nm and 35 nm, respectively; after increasing one SiO2 coating layer, the shell thickness was increased to 26 nm and 52 nm, respectively. The release profiles showed that the drug release decreased with increase of shell thickness. The release amount of FITC from thinner thermosensitive silica hollow spheres in 200 nm diameter is 86% at 25°C and 57% at 40°C, and decreasing to 80% and 25% after one additional layer coating, respectively. The result was also found in thermosensitive silica hollow spheres in 600 nm diameter, showing that the shell thickness is one of the main controlling factors for the system. In addition, the temperature also affect the release rate showed that PNIPAM play an important role in controlling release process.

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 二氧化矽 4
2-1-1 溶膠-凝膠之定義 4
2-1-2 溶膠-凝膠法之反應機制 5
2-1-3 溶膠-凝膠法製備二氧化矽奈米顆粒之影響因素 5
2-1-4 二氧化矽之生物相容性 6
2-2 核-殼結構顆粒之製備 10
2-3中空結構顆粒 14
2-4智慧型高分子 16
2-4-1智慧型高分子的種類 16
2-4-2 聚異丙基丙烯醯胺 18
2-5 藥物控制釋放 24
2-5-1 藥物控制釋放機制 24
2-5-2 載體型態對於藥物釋放行為之影響 25
2-5-3 溫度對於藥物釋放行為之影響 29
2-5-4 pH值對於藥物釋放行為之影響 32
第三章 實驗方法與步驟 33
3-1 實驗材料 33
3-2 實驗儀器 37
3-3 實驗架構 39
3-4實驗步驟 40
3-4-1聚苯乙烯球之製備 40
3-4-2 聚苯乙烯球表面改質 41
3-4-3 二氧化矽奈米顆粒前驅物之製備 42
3-4-4 聚苯乙烯球/二氧化矽核殼顆粒之製備 43
3-4-5 二氧化矽中空球之製備 44
3-4-6 聚異丙基丙烯醯胺接枝二氧化矽中空球之製備 45
3-4-7 聚異丙基丙烯醯胺接枝二氧化矽中空球之藥物釋放模擬 46
3-5 材料性質分析 47
3-6-1 傅利葉轉換紅外線光譜儀( FTIR ) 47
3-6-2 動態光散射儀( DLS ) 47
3-6-3 場發射掃描式電子顯微鏡( FE-SEM ) 47
3-6-4 穿透式電子顯微鏡( TEM ) 47
3-6-5 微差熱掃描熱分析儀( DSC ) 48
3-6-6 紫外光可見光譜儀(UV-vis ) 48
3-6-7 X射線電子能譜儀(XPS) 48
3-7實驗樣品及其代號 49
第四章 結果與討論 50
4-1聚苯乙烯球模板與二氧化矽奈米顆粒之製備與特性 50
4-2 聚苯乙烯球之表面電位改質 54
4-3 聚苯乙烯-二氧化矽/核-殼顆粒之製備與特性分析 58
4-4 二氧化矽中空球之製備與特性分析 63
4-5 聚異丙基丙烯醯胺接枝二氧化矽中空球之製備與特性分析 67
4-6 藥物吸附與釋放試驗 72
4-6-1 殼層厚度對於藥物釋放行為的影響 77
第五章 結果與討論 82
參考文獻 83

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