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研究生： 余政倫
Yu, Cheng-lun
論文名稱： 以聚乙烯二醇修飾之奈米磁性微脂粒之熱效應探討
Polyethylene glycol modified phospholipid-nanomagnetic particles for the investigation of thermal effect
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： 2008
畢業學年度： 96
語文別： 中文
論文頁數： 83
中文關鍵詞： 太平洋紫杉醇 、熱效應 、二氧化矽 、奈米磁性粒子 、微脂粒
外文關鍵詞： nanomagnetic particle, liposome, silica, thermal effect, paclitaxel
相關次數： 點閱：126  下載：2 
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    • 隨著奈米生物科技的急速發展，奈米磁性材料被廣泛應用於生物醫學技術之中；其獨特之小尺寸及超順磁特性，適與其他生物相容性材料結合為奈米磁性複合粒子，在外加磁場下可作為藥物載體進行靶向治療，並配合產生之熱效應，對腫瘤細胞的治療極具研究價值。本研究將分別製備與探討奈米磁性複合材料之磁性微脂粒與磁性二氧化矽顆粒，並進一步研究其於外加磁場下的熱效應；最後測試其用作藥物載體時對太平洋紫杉醇(paclitaxel)之攜帶與釋放行為。

    本研究以共沉澱法合成奈米磁性粒子，並以穿透式電子顯微鏡(transmission electron microscopy, TEM)觀察其平均粒徑約9 nm；而經過磷脂膽鹼(1,2-dipalmitoyl-sn-glycero-3-phocholine, DPPC)修飾，可提升奈米磁性粒子在有機溶劑中的分散效果；另外檸檬酸的修飾則可以避免奈米磁性粒子在水溶液中的聚集情形。進一步以聚乙烯二醇與磷脂乙醇胺(1,2-dimytistoyl-sn-glycerol-3-phosphoethanolamine, DMPE)反應合成之PEG-DMPE複合物製備磁性微脂粒，並以TEM觀察其粒子形態。

    除此之外，以溶膠凝膠法合成磁性二氧化矽顆粒，以奈米磁性粒子為成長晶核，使四以氧基矽烷(tetraethoxysilane, TEOS)沿其表面向外成長，得到包覆奈米磁性粒子之磁性二氧化矽顆粒。經TEM影像分析，確知二氧化矽顆粒確有包覆奈米磁性粒子的能力。

    在本研究中，探討奈米磁性粒子、磁性微脂粒與磁性二氧化矽顆粒在外加磁場下之升溫能力，以了解未來熱治療的可行性。太平洋紫杉醇為一種口服無療效且極難溶於水的抗癌藥物，必須以特殊溶劑進行投藥，但使用之溶劑往往會引發嚴重的副作用；故本研究以所製備之奈米複合材料做為此藥物之載體，探討其包覆與釋放藥物的能力。

    Nano-biotechnology can improve the developments on biomedicine. Nanomagnetic particle has attracted a lot of attentions because of their potential for hyperthermia anticancer treatment and drug carriers. In this study, magnetic liposome and magnetic silica were synthesized and characterized. By applying the electromagnetic field, temperature raised by the nanomagnetic materials was induced and monitored by the optical fiber thermometer. Additionally, paclitaxel, and effective drug in treating a variety of cancers was encapsulated in the liposome and silica particle.

    Nanomagnetic particle was synthesized by co-precipitation and the average size of the Fe3O4 nanoparticles was about 9 nm which could be observed by transmission electron microscopy (TEM). Upon the modification with DPPC (1,2-dialmitoyl-sn-glycero-3-phosphocholine), the nanoparticles could achieve much better dispersion in organic solution. On the other hand, the nanomagnetic particle was also stabilized by citric acid to avoid aggregation in water solution.The PEG (polyethylene glycol) modified nanomagnetic liposome was prepared and the TEM images of magnetic liposome were observed. In this work, DMPE (1,2-dimytistoyl-sn-glycerol-3-phosphoethanolamine) was mixed with PEG to from the PEG-DMPE. The PEG-DMPE was further used to synthesize the PEG modified magnetic liposome.

    The magnetic silica particle was synthesized by the so-gel method, coating nanomagnetic particle with silica by using magnetic fluids as seeds. Silica was formed on the surface of nanomagnetic particle through by hydrolysis and condensation of TEOS (tetraethoxysilane).

    In this research, the nanomagnetic complexes were also exposed to an alternative magnetic field for the investigation of thermal effect, which is regarded to be one of the promising approaches in cancer therapy. Paclitaxel is orally inactive and has extremely low aqueous solubility. Inclusion of paclitaxel in liposomal formulations or silica particle has proved to be a good approach to improve the drug’s antitumor efficacy.

    中文摘要 I Abstract II 誌謝 III 總目錄 IV 表目錄 VII 圖目錄 VIII 第一章 緒論 1 1-1 奈米科技 1 1-1-1 奈米粒子的特性 1 1-1-2 奈米粒子的製備方式 2 1-1-3 奈米粒子的應用範圍 3 1-2 磁性奈米粒子 4 1-2-1 奈米磁性粒子的特性 4 1-2-2 奈米磁性粒子的製備方式 6 1-2-3 奈米磁性粒子的表面修飾 6 1-2-4 奈米磁性粒子在生醫材料上的應用 9 1-3 生物膜(biomembranes)及微脂粒(liposome) 11 1-3-1 磷脂質與微脂粒 11 1-3-2 微脂粒的製備與性質 12 1-3-3 微脂粒的表面修飾 14 1-3-4 磁性微脂粒 15 1-4 高分子與二氧化矽顆粒 16 1-4-1 高分子聚合物包覆技術 16 1-4-2 奈米磁性二氧化矽顆粒 17 1-5 太平洋紫杉醇 17 1-6 研究動機與目的 19 第二章 實驗材料與方法 20 2-1 奈米磁性粒子之製備及表面修飾 20 2-1-1 製備奈米磁性粒子 20 2-1-2 以磷脂膽鹼修飾奈米磁性粒子 21 2-1-3 以檸檬酸修飾奈米磁性粒子 22 2-2 微脂粒之製備及表面修飾 23 2-2-1 微脂粒之表面修飾 23 2-2-2 製備微脂粒 24 2-2-3 製備磁性微脂粒 25 2-2-4 製備包覆太平洋紫杉醇之微脂粒 26 2-2-5 製備包覆太平洋紫杉醇之磁性微脂粒 27 2-3 二氧化矽顆粒之製備 28 2-3-1 製備二氧化矽顆粒 28 2-3-2 製備磁性二氧化矽顆粒 29 2-3-3 製備攜帶太平洋紫杉醇之二氧化矽顆粒 29 2-3-4 製備攜帶太平洋紫杉醇之磁性二氧化矽顆粒 29 2-4 奈米磁性材料之熱治療效應分析 30 2-4-1 奈米磁性粒子之熱治療效應分析 30 2-5 太平洋紫杉醇之包覆及釋放行為分析 31 2-5-1 太平洋紫杉醇之定量分析 31 2-5-2 磁性及非磁性微脂粒包覆太平洋紫杉醇之釋放行為 31 2-5-3 磁性及非磁性二氧化矽包覆太平洋紫杉醇之釋放行為 31 2-6 相關儀器分析 32 2-6-1 穿透式電子顯微鏡 32 2-6-2 X射線繞射儀 32 2-6-3 超導量子干涉儀 33 2-6-4 液相層析儀 33 2-7 實驗藥品 35 2-8 實驗儀器 36 第三章 結果與討論 37 3-1 奈米磁性粒子的製備及表面修飾 37 3-1-1 奈米磁性粒子之TEM影像分析 37 3-1-2 奈米磁性粒子之X光繞射儀分析物性鑑定 40 3-1-3 奈米磁性粒子之磁性分析 42 3-2 磁性及非磁性微脂粒的製備 44 3-2-1 磁性及非磁性微脂粒之影像分析 44 3-2-2 磁性微脂粒之磁性分析 50 3-3 磁性及非磁性奈米二氧化矽顆粒的製備 51 3-3-1 磁性及非磁性奈米二氧化矽顆粒之TEM影像分析 51 3-4 奈米磁性粒子之熱治療效應分析 55 3-4-1 未修飾奈米磁性粒子 55 3-4-2 以磷脂膽鹼修飾之奈米磁性粒子 59 3-4-3 以檸檬酸修飾之奈米磁性粒子 60 3-5 磁性微脂粒之熱效應分析 65 3-5-1 不同濃度磁性微脂粒之熱效應分析 65 3-6 磁性二氧化矽顆粒之熱效應分析 68 3-6-1 不同濃度磁性二氧化矽顆粒之熱效應分析 68 3-7 太平洋紫杉醇之攜帶與釋放行為分析 71 3-7-1磁性及非磁性微脂粒對太平洋紫杉醇之釋放行為 71 3-7-2磁性及非磁性二氧化矽對太平洋紫杉醇之攜帶與釋放行為 74 第四章 結論 77 參考文獻 79 作者自述 83

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