碩博士論文 84341006 詳細資訊


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姓名 傅佑璋(Ywu-Jang Fu)
查詢紙本館藏  
電子郵件信箱 E-mail 資料不公開
畢業系所 化學工程與材料工程研究所(Chemical and Materials Engineering)
畢業學位 博士(Ph.D.) 畢業時期 089學年第2學期
論文名稱(中) 聚乳酸(PLA)及乳酸/羥基乙酸共聚合物(PLGA)
於抗癌藥物傳輸系統之研究
論文名稱(英) The study of polylactide and Polylactide-co-glycolide in the anti-cancer drugs delivery stem
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論文語文/頁數 中文/179
摘要(中) 本研究是以聚乳酸(Polylactide)及其共聚物乳酸羥基乙酸(Polylactide-co-glycolide)為高分子基質製備藥物輸送系統,以應用於抗癌藥物之控制釋放,研究利用噴霧乾燥技術製備具有控制釋放特性之微膠囊。研究結果顯示噴霧乾燥技術能製備出粒徑為1~10 mm的微小球(microspheres),並可由壓縮空氣流率控制其粒徑分佈,藉由最適製備參數調整最高能獲得50 % 的產率。藥物含量的分析結果顯示大部分微膠囊的藥物含量均趨近理論值的藥物含量。參數設計統計法對實驗結果的分析可知微膠囊的性質受噴霧乾燥器進料溫度、聚乳酸濃度以及空氣流率影響最顯著。藥物釋放實驗的結果顯示噴霧乾燥技術所製得的微膠囊能持續藥物的釋放達7天以上。研究並發展水溶性抗癌藥物,5-Fluorouracil (5-FU)以噴物乾燥技術包覆於PLGA基質以應用於控制釋放系統,以二氯甲烷/氯仿/甲醇( 1:1:2 V / V )之混合溶劑可製得近球形具緻密層的微膠囊,結果得知微膠囊平均粒徑約2μm,藥物包覆含量約9%,而LA/GA比對藥物之控制釋放是非常重要的影響因素;經最適製程條件產出之微膠囊有良好之表面形態,包覆效率可達90%以上。並藉由高分子基質之LA/GA比例,討論不同釋放時間藥物之釋放模式,使藥物釋出之擴散路徑長度(藥物釋放速率)呈固定常數值,而符合零次釋放之達成。本研究製得之微膠囊藉由血小板吸附實驗評估PLA及PLGA 基質經製備程序後之生物相容性。並利用人類口腔癌細胞(KB) 與包覆抗癌藥物微膠囊之釋放液進行細胞培養實驗,經MTT比色分析,可証明抗癌藥物的釋放作用確實具有抑制人類口腔癌細胞(KB)增生繁殖,而達到有效的治療效果。
摘要(英) The purpose of this study is to design the drug delivery system by using polylactide and poly (D, L-lactide-co-golycolide) as a polymeric matrix, and apply the devised to controlling the release of anticancer drugs. Research in this study has developed various drug delivery media by spray drying technique. The controlled release microspheres were prepared by spray drying and investigate several process parameters that can affect the characteristics of microspheres. Normal size distribution with diameters ranging from 1 to 10μm was obtained by spray drying technique. A higher yield of microspheres was recovered depending on polymer solution and process conditions employed. Results show that the yield of microspheres could reach 50% and the experimental drug loading approached to the theoretical drug loading. A factorial design approach was used to optimize conditions to produce microcapsules. The main factors affecting spray drying were found to be the initial temperature, polymer concentration and air flow. The in-vitro release of anticancer drug from microspheres sustained over seven days. Then we describe the water soluble anti-cancer drug, 5-Fluorouracil (5-FU) is encapsulated into biodegradable copoly (dl-lactic/glycolic acid)(PLGA) using spray drying method for the development of long-lasting controlled release systems. The mixture of dichloromethane/chloroform/methanol (1:1:2 v/v) resulted in the modification of morphology, while the physical structure of the microsphere varied from a porous PLGA microsphere to a dense PLGA microsphere. The results show that the average diameter was 2mm and anticancer drug loading of microspheres approached approximately 9 % (w/w). Encapsulation efficiency was reached up 90%,depending on the microsphere best formulation. In addition, the lactide/glycolide ratio of the polymer is an important parameter for controlling the release profile of the entrapped anticancer drug. Finally, the blood compatibility of PLA and PLGA samples were estimated in biocompatibility after prepared process. In use of the method of MTT assay, we could confirm the inhibiting proliferation of KB by the releasing anticancer drug and effective therapy to cancer in vitro.
關鍵字(中)
  • 乳酸/羥基乙酸共聚合物
  • 噴霧乾燥法
  • 微膠囊
  • 抗癌藥物
  • 控制釋放
  • 產率
  • 聚乳酸
  • 藥物傳輸系統
  • 關鍵字(英)
  • polylactide
  • Polylactide-co-glycol
  • spray drying
  • 論文目次 封面
    中文摘要
    英文摘要
    目錄
    圖目錄
    表目錄
    第一章 緒論
    第二章 文獻回顧
    2.1 藥物之包覆技術
    2.2 包覆材質
    2.3 抗癌藥物及其作用機轉
    2.4 釋放動力學
    第三章 以噴霧乾燥法製備非水溶性抗癌藥物之聚乳酸微膠囊及其藥物釋放特性
    3.1 前言
    3.2 實驗
    3.3 結果與討論
    3.4 結論
    第四章 以噴霧乾燥法製備水溶性藥物之乳酸/羥基乙酸共聚合物(PLGA)微膠囊及其藥物釋放特性
    4.1 前言
    4.2 藥品與儀器
    4.3 實驗
    4.4 結果與討論
    4.5 結論
    第五章 聚乳酸及其共聚物植入物之製備及釋放特性分析
    5.1 前言
    5.2 實驗
    5.3 結果與討論
    5.4 結論
    第六章 抗癌藥物載體於生物相容性及癌細胞毒性之評估
    6.1 前言
    6.2 實驗
    6.3 結果與討論
    6.4 結論
    第七章 總結論
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    指導教授
  • 徐新興 (Shin-Shing Shyu)
  • 口試日期 2001-07-06 繳交日期 2001-07-06

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