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論文中文名稱:磁性幾丁聚醣奈米粒子包覆喜樹鹼之研究 [以論文名稱查詢館藏系統]
論文英文名稱:Magnetic chitosan nanoparticles for camptothecin delivery [以論文名稱查詢館藏系統]
院校名稱:臺北科技大學
學院名稱:工程學院
系所名稱:化學工程研究所
畢業學年度:101
出版年度:102
中文姓名:李新和
英文姓名:Hsin-Ho Li
研究生學號:98738038
學位類別:碩士
語文別:中文
口試日期:2013-07-25
論文頁數:71
指導教授中文名:林忻怡
口試委員中文名:鍾仁傑;謝學真
中文關鍵詞:奈米磁珠檸檬酸鈉幾丁聚醣喜樹鹼
英文關鍵詞:Iron oxide nanoparticlesSodium citrateChitosanCamptothecin
論文中文摘要:此研究應用智慧型載體的設計概念與癌症化學治療作結合,使藥物載體具有磁導功能,並以天然高分子幾丁聚醣 (Chitosan, Cs) 包覆在外,使化療藥物喜樹鹼(Camptothecin, CPT)延緩藥物釋放,並且在患部給予外加磁場,提高患部藥物濃度,降低其他器官的藥物濃度,減少化療可能發生之副作用。
合成原理先以檸檬酸鈉(Sodium citrate)當作界面活性劑修飾奈米磁珠(Iron oxide nanoparticles,Fe3O4)表面時,因為官能基的解離而使粒子帶有表面負電荷。利用相異電荷相吸原理,使帶有正電荷幾丁聚醣包覆奈米磁珠(CS/Fe3O4)。之後再利用喜樹鹼因PH值由鹼變中性,此時水溶性的喜樹鹼carboxylate會轉換成非水溶性的lactone,吸附在幾丁聚醣包覆奈米磁珠裡(CPT/CS/Fe3O4)。
實驗結果得知藥物載體粒徑約 300nm,在藥物負載率方面能達到 41% 左右。體外藥物釋放數據也顯示,在有外加磁場下,的確能有效加速藥物的釋放。細胞毒性測試結果也證實,CS/Fe3O4對細胞並沒有毒殺效果,而CPT/CS/Fe3O4與CS/Fe3O4相較下,明顯提高了對癌細胞的毒殺效果。多項結果都能表示智慧型藥物載體在未來化療領域更有應用與研究價值。
論文英文摘要:he purposes of this study for the multifunctional nanoparticles -mediated cancer chemotherapy drug delivery, their multifunction includes the following steps. Firstly, the drug carrier can be controlled by superparamagnetism. Secondly, the chemotherapy drug (Camptothecin, CPT) was adsorbed in the natural polymeric carrier to form nanoparticles with low toxicity. We developed the new purpose of the multifunctional
chitosan (Cs) nanoparticles-mediated CPT release for cancer therapy.
Surface modification of Fe3O4 nanoparticles was carried out by treating the nanoparticles with sodium citrate. Because dissociation of functional groups with particles leaving the negative surface charge. Using dissimilarity charges attract principles, then positive charge of chitosan coated Fe3O4 nanoparticles (CS/ Fe3O4). Water-soluble CPT carboxylate converted into its water-insoluble lactone form due to the acidification with decreasing pH. The lactone-formed CPT was immediately precipitated and adsorbed to the chitosan coated Fe3O4 nanoparticles.
According to the results, the CPT/CS/Fe3O4 was nanoscale of particle size (around 300 nm) but with low drug loading efficiency (above 41%). In vitro drug release data show that it can effectively accelerate the drug release under an external magnetic field. Cytotoxicity test results also confirmed, the CS/ Fe3O4 is low toxic effect on cancer cells, but the CPT/CS/ Fe3O4 is higher toxic effect on cancer cells. The CPT/CS/ Fe3O4 constitutes a useful approach for the future design of drug carriers.
論文目次:摘 要 i
ABSTRACT ii
誌 謝 iii
目 錄 iv
表目錄 vi
圖目錄 vii
第一章 緒論 1
1.1 前言 1
1.2 研究目的 2
第二章 文獻回顧 3
2.1 奈米科技 3
2.1.1 奈米簡介 3
2.1.2 奈米材料的特性 4
2.1.3 奈米粒子的應用 5
2.2 磁性奈米粒子 6
2.3 磁學原理 7
2.3.1 磁性之分類 9
2.3.2 氧化鐵的種類 10
2.4 幾丁聚醣(Chitosan) 19
2.5 喜樹鹼 Camptothecin(CPT) 21
第三章 實驗材料與方法 22
3.1 實驗材料 22
3.1.1 細胞來源 22
3.1.2 細胞培養用藥品 22
3.1.3 實驗藥品 23
3.1.4 儀器設備 25
3.1.5 藥品及溶液製備 28
3.2 實驗方法 30
3.2.1 實驗設計 30
3.2.2 實驗流程 31
3.2.3 磁性奈米藥物載體物理性質測試 33
3.2.4 磁性奈米藥物載體細胞活性測試 36
3.2.5 統計分析 39
第四章 結果與討論 40
4.1 磁性奈米藥物載體物外觀 40
4.2 磁性奈米藥物載體物理性質測試 42
4.2.1 穿透式電子顯微鏡(TEM) 42
4.2.2 磁性奈米藥物載體單顆粒徑分析 44
4.2.3 動態光散射粒徑分析(DLS) 47
4.2.4 Zeta表面電位量測 48
4.2.5紅外線光譜測量(FTIR) 49
4.2.6磁特性量測(VSM) 51
4.2.7 Drug loading percent and drug loading efficiency 53
4.2.8 藥物釋放(CPT/CS/mNPs release) 54
4.3 磁性奈米藥物載體細胞活性測試 55
4.3.1 細胞毒性測試(Cytotoxicity) 55
4.3.2 磁場標定 61
4.3.3普魯士藍切片染色(Prussian blue staining) 63
第五章 結論 65
參考文獻 66
附錄 70
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