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研究生: 洪碩延
Hong, Shou-Yan
論文名稱: 具標靶性之環糊精包覆磁性奈米顆粒之鑑定與其熱效應及裝載辣椒鹼之探討
Identification and preparation of targeted cyclodextrin magnetic nanoparticles for thermal effect and the investigation on the loading of capsaicin
指導教授: 許梅娟
Syu, Mei-Jywan
學位類別: 碩士
Master
系所名稱: 工學院 - 化學工程學系
Department of Chemical Engineering
論文出版年: 2011
畢業學年度: 99
語文別: 中文
論文頁數: 91
中文關鍵詞: 磁性奈米粒子β-環狀糊精亞麻油酸藥物釋放
外文關鍵詞: magnetic nanoparticle, β- cyclodextrin, linoleic acid, drug release
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  • 磁性奈米材料相關的研究已廣泛地應用於生物醫學上。由於其超順磁特性及低生物毒性,在外加磁場下,可作為體內傳遞藥物的載體,並因其熱效應,能夠有效地抑制或除去癌細胞,更以標靶癌細胞的方式,可使藥物及熱治療直接對位到癌細胞。
    本研究是以水相共沉澱法製備磁性奈米粒子,在其外層包覆β-環糊精 (β-cyclodextrin, β-CD) 及亞麻油酸 (linoleic acid),以探討奈米磁球的熱效應;並以環糊精疏水性的中孔包覆抗癌藥物,而亞麻油酸可標靶肝細胞。以XRD (X-ray diffractometer) 確認奈米磁粒為Fe3O4之晶相,而利用FT-IR (Fourier Transform Infrared Spectrophotometer) 與TGA (Termogravimetric Analysis) 鑑定β-CD及亞麻油酸已修飾於其上,並以TEM (Transmission Electron Microscope) 影像分析估算Fe3O4、Fe3O4@β-CD及Fe3O4@β-CD-LA粒子之平均微晶尺寸,分別為8.87  4.43 nm、9.97  3.86 nm與11.28  1.52 nm。由磁性分析之磁滯曲線可以得知Fe3O4、Fe3O4@β-CD及Fe3O4@β-CD-LA的飽和磁化量分別為84.51 emu/g、68.24 emu/g與27.89 emu/g。繼之將奈米磁球進行滅菌,探討滅菌後對組織細胞的影響。已有文獻指出capsaicin對癌細胞有明顯的抑制效果,特別是前列腺癌細胞,因此也進行修飾後的奈米磁球對包覆capsaicin以及釋放的探討。
    奈米裸磁粒在施加高頻磁場下,於10分鐘內可達90oC,在50分鐘內可達100 oC;而經由β-CD包覆後,則10分鐘內可達72oC;而經由β-CD與亞麻油酸修飾後則在10分鐘內可達66oC,顯示經包覆後的奈米磁粒,其熱效應明顯下降,但還是具有良好之效果足以進行對腫瘤細胞之熱治療。而經過滅菌後的奈米磁性粒子於10分鐘高頻磁場下分別可達94 oC (Fe3O4),68 oC (Fe3O4@β-CD),以及64 oC (Fe3O4@β-CD-LA),顯示滅菌後依然具有良好熱治療效果。

    The research of magnetic nanoparticles has been extensively applied to biologically medical technology for several years. The nanoparticles can be used as a drug carrier due to their size-dependent superparamagnetism and low cytotoxicity. Additionally, their hyperthermia anticancer treatment can depress or kill the cancer cells. And the use of targeting technique makes the drug and hyperthermia treatment directly affects the cancer cells.
    In this study, the magnetic nanoparticles were synthesized by co-precipitation. The surface of nanoparticles was further modified with β-cyclodextrin and linoleic acid. Cyclodextrin, known to be a good host for the inclusion of guest molecule. Linoleic acid can be used to target hepatocytes. The thermal effect of the magnetic nanoparticles under applied magnetic field was also investigated. We used XRD to confirm the Fe3O4 structure of magnetic nanoparticles, and the modification by β-CD and linoleic acid was confirmed by TGA and FT-IR. The size of Fe3O4、Fe3O4@β-CD and Fe3O4@β-CD-LA were estimated to be 8.87  4.43 nm、9.97  3.86 nm and 11.28  1.52 nm, respectively, which were observed and calculated by TEM. SQUID results indicated that saturation magnetization of Fe3O4 、Fe3O4@β-CD and Fe3O4@β-CD-LA were 84.51 emu/g 、68.24 emu/g and 27.89 emu/g, respectively. Then we proceed to sterilization by autoclave and investigate the influence on tissue cells. Some researches have showed that capsaicin can depress the cancer cells, especially prostate cancer cells. So we also investigated the loading and releasing efficiency of capsaicin.
    Under applied magnetic field, temperature of bare magnetic nanoparticles could increase up to 90 oC in 10 min and 100 oC in 50 min. With the modification of the nanoparticles with β-CD, the temperature could increase to 72 oC in 10 min. And with the modification of the nanoparticles with β-CD-LA, the temperature could increase to 66 oC in 10 min. The thermal effect of magnetic nanoparticles with modification could remarkably decrease, but they still have excellent hyperthermia effect toward cancer cells.

    中文摘要……………………………………………………………………………… I Abstract………………………………………………………………………………. II 目錄…………………………………………………………………………………..III 表目錄……………………………………………………………………………..... VI 圖目錄……………………………………………………………………………....VII 第一章 緒論…………………………………………………………………………..1 1-1奈米材料簡介………………………………………………………………….1 1-1-1 奈米材料的特性………………………………………………………….1 1-1-2 磁性奈米材料…………………………………………………………….5 1-1-3 磁性奈米粒子的製備…………………………………………………….6 1-1-4 磁性奈米粒子之表面修飾……………………………………………….8 1-1-5 磁性奈米粒子在生物醫學上的應用…………………………………….9 1-2 環狀糊精…………………………………………….………………………..14 1-2-1 環狀糊精的結構特性…………………………………………………...14 1-2-2 環狀糊精在藥物釋放上的釋放………………………………………...16 1-3 亞麻油酸……………………………………………………………………...17 1-3-1 亞麻油酸的基本性質…………………………………………………...17 1-3-2 亞麻油酸於生醫上的應用……………………………………………...17 1-3-3 肝細胞…………………………………………………………………...18 1-3-4 肝細胞標靶之發展……………………………………………………...19 1-4 研究動機與目的……………………………………………………………...20 第二章 實驗方法與材料…………………………………………………………..21 2-1 實驗合成步驟之概述………………………………………………………...21 2-1-1 磁性奈米粒子 (Fe3O4) 之製備………………………………………...21 2-1-2 Fe3O4@β-CD之製備…………………………………………………….21 2-1-3 Fe3O4@β-CD-LA之製備.........................23 2-2 磁性奈米粒子之熱效應分析………………………………………………...25 2-3 藥物包覆與釋放之流程……………………………………………………...25 2-3-1 Capsaicin 之定量分析方法……………………………………………..25 2-3-2 藥物包覆流程…………………………………..……………………….25 2-3-3 藥物釋放流程……………………………………..…………………….26 2-4 相關儀器分析及樣品製備…………………………………………………..26 2-4-1 穿透式電子顯微鏡 (Transmission Electron Microscope, TEM)…....…26 2-4-2 掃描式電子顯微鏡 (Scanning Electron Microscope, SEM)….…....…..27 2-4-3 高週波感應加熱機……………………………..……………………….27 2-4-4 X-ray 繞射儀 (X-ray diffractometer, XRD)…………..………………...27 2-4-5 超導量子干涉儀 (SQUID)……………………………..…..…………..28 2-4-6 熱重分析儀 (Termogravimetric Analysis, TGA)………………...….….28 2-4-7 傅立葉紅外線光譜儀 (FT-IR)……………………...…………………..29 2-4-8 元素分析儀 (Elemental Analysis, EA)………………...……………….29 2-4-9 奈米粒徑電位分析儀 (Nano Zeta Sizer)……………………………….29 2-5 實驗藥品……………………………………..……………………………….30 2-6 實驗儀器……………………………………..……………………………….31 第三章 結果與討論…………………………………………………………………32 3-1 磁性奈米粒子 (Fe3O4) 的製備與其表面修飾…………….……………….32 3-1-1 穿透式電子顯微鏡 (TEM) 進行奈米磁球之影像分析……..………..34 3-1-2 XRD之分析圖譜……………………………………..………………….47 3-1-2 FT-IR分析……………………………………..…………………………51 3-1-4 熱重分析儀 (TGA) 分析………………………………………………63 3-1-5 元素分析………………………………………...………………………65 3-1-6 磁性奈米粒子之磁性分析……………………..……………………….65 3-1-7 粒徑分析………………………………………..……………………….70 3-2 磁性奈米粒子熱效應之探討…………………...……………………………71 3-3 Fe3O4@β-CD-LA磁性奈米粒子包覆 capsaicin藥物之探討……………….77 第四章 結論…………………………………………………………………………86 參考文獻……………………………………………………………………………..87

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