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研究生:魏宗平
研究生(外文):Tzung-Ping Wei
論文名稱:PLGA 微球包覆 Rapamycin 與蠶絲蛋白/明膠形成複合薄膜之藥物釋放探討
論文名稱(外文):Drug Release of PLGA Microsphere Entrapment Rapamycin Packed in Fibroin-gelatin Composite Films Fembrane
指導教授:蘇文達蘇文達引用關係
指導教授(外文):Wen-Ta Su
口試委員:劉席瑋蔡德華
口試委員(外文):Hsia-Wei LiuTeh-Hua Tsai
口試日期:2012-06-28
學位類別:碩士
校院名稱:國立臺北科技大學
系所名稱:化學工程研究所
學門:工程學門
學類:化學工程學類
論文種類:學術論文
論文出版年:2012
畢業學年度:100
語文別:中文
論文頁數:75
中文關鍵詞:PLGA微粒雷帕黴素藥物釋放蠶絲蛋白
外文關鍵詞:PLGAparticlesRapamycindrugreleasesilk
相關次數:
  • 被引用被引用:6
  • 點閱點閱:367
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  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
微米粒子在藥物傳遞系統上,有保護藥物活性、標靶給藥、控制釋放速率等眾多優勢。聚乳酸與聚甘醇酸共聚物(poly (DL-lactide-co-glycolide),PLGA)為生物可分解高分子,常使用於生醫工程上,藉由乳酸與甘醇酸的莫爾比例調整,可調控高分子性質。雷帕黴素(Rapamycin)在臨床上,有抑制免疫反應與抗發炎的療效,也能抑制癌細胞有絲分裂,達到抗癌效果。在老鼠活體實驗的文獻中也指出能使神經細胞再生,促進脊神經修復。本實驗將Rapamycin包覆於PLGA微粒中,再將PLGA微粒鑲入多層蠶絲蛋白與明膠複合膜中,藉由調整蠶絲蛋白與明膠比例,控制藥物釋放速率。
以乳化蒸散法製作微粒,粒徑大小與形貌經掃描式電子顯微鏡觀察,直徑約10μm,以分光光度計(278nm)測得包藥率為43.4%,經30天累積藥物釋率放可達98.6%。若把微粒包埋在1:1ヽ2:1ヽ4:1的蠶絲蛋白與明膠混合比例複合膜中,經30天累積釋放率分別為84.9%ヽ74.7%ヽ67.4%,此包覆法能有效緩慢釋放出Rapamycin,並改善一般載體有藥物突釋的現象。


Nanoparticle has a wide range of advantages to protect active pharmaceutical ingredient, targeted medicine as well as control release rate in the drug delivery system. PLGA is biodegradable high polymer and commonly-used in biomedical tissue engineering by the mole ratio adjustment between lactic acid and glycolic acid in order to control high polymer ability. Rapamycin clinically inhibit immunological reaction and cure anti-inflammatory as well as inhibit cancer cells mitotic that will reach anti-cancer effect. This experiment will be focused on including Rapamycin into PLGA and making PLGA into multi-layer fibroin and synthesized thin films. Then, with the ratio adjustment between fibroin and synthesized thin film, we will make controlled drug release ratio.
With solvent evaporation method, we analyze how to make particles and what the particle size and shape like by electron microscope with 10cm diameter. We examine the medication package of 43.4% from UV spectrometers and the accumulated drug release rate can reach at 98.61% in thirty days. With the mixed ratio of fibroin and synthesized thin films in the particles for 1:1ヽ2:1ヽ4:1, the total accumulated release rate will be 84.9%ヽ74.7%ヽ67.4% individually. This package method can release Rapamycin slowly but effectively that will improve drug burst phenomenon.


目 錄
中文摘要 I
英文摘要 II
誌謝 III
目錄 VI
表目錄 IX
圖目錄 X
第一章 緒論
1.1 前言 1
1.2 研究目的 2
第二章 文獻回顧 3
2.1 神經系統 3
 2.1.2 神經細胞 4
 2.1.3 神經訊息傳遞 4
 2.1.4 脊髓損傷 5
2.2 藥物釋放 6
 2.2.1 藥物傳輸系統 8
  2.2.1.1 擴散釋放 9
  2.2.1.2 膨脹釋放 9
  2.2.1.3 溶蝕釋放 10
 2.2.2 微粒藥物載體簡介 11
  2.2.2.1 微脂體 11
  2.2.2.2 金屬微粒 12
  2.2.2.3 高分子微粒 12
  2.2.2.4 高分子偶聯藥物微粒 12
  2.2.2.5 樹狀聚合物微粒 12
  2.2.2.6 聚合物微胞 13
 2.2.3 微粒藥物載體簡介 13
  2.2.3.1 溶液乳化蒸發法製備微粒 15
  2.2.3.2 包覆率 16
  2.2.3.3 控制微粒粒徑大小 17
  2.2.3.4 控制藥物釋放速率的因素 17
2.3 組織工程 19
2.4 生物可降解性材料簡介 21
 2.4.1 Poly(D,L-lactide-co-glycolide),PLGA簡介 25
  2.4.1.1聚乳酸與聚甘醇酸共聚物(PLGA)合成 26
 2.4.2 蠶絲蛋白簡介 27
 2.4.3 明膠簡介 29
2.5 the layer-by-layer (LbL)簡介 29
2.6 Rapamycin簡介 30
2.7 mTOR(mammalian target of rapamycin)抑制機制 31
2.8 Rapamycin對神經修復的因素 34
2.9 藥物釋放數學模式 36
2.9.1 零階動力模式 36
2.9.2 一階動力學模式 36
2.9.3 Higuchi 基質動力學模式 38
第三章 實驗設備、藥品、流程 39
3.1 實驗相關設備及廠牌 39
 3.1.1 實驗設備 39
 3.1.2 實驗器材 39
3.2實驗使用藥品 40
3.3實驗流程 42
第四章 實驗方法 43
4.1 純化蠶絲蛋白 43
4.2 PLGA微粒製作 43
4.3蠶絲蛋白/明膠包覆微粒薄膜製作 44
4.4蠶絲蛋白/明膠薄膜機械測試 44
4.5蠶絲蛋白/明膠體外生物分解速率測試 45
4.6微粒包覆率 46
4.7微粒體外累積釋放率 46
4.8蠶絲蛋白/明膠包覆微粒薄膜體外累積釋放 47
4.9材料表面結構 48
 4.9.1 掃描式電子顯微鏡探究PLGA微粒表面形態 48
 4.9.2掃描式電子顯微鏡探究蠶絲蛋白/明膠薄膜表面形態 48
 4.9.3探究蠶絲蛋白/明膠薄膜之微粒散布樣貌 48
 4.9.4光學顯微鏡觀察PLGA微粒 48
4.10雷射光散射粒徑分析儀 48
第五章 結果與討論 50
5.1薄膜機械性質 50
5.2薄膜體外重量損失率 51
5.3微粒包覆率 52
5.4微粒體外釋放率 53
5.5微粒散布形態 54
5.6複合膜體外釋放率 55
5.7材料表面形態 56
 5.7.1微粒表面形態 56
 5.7.2光學顯微鏡觀察 57
 5.7.3粒徑分析 60
 5.7.4單獨微粒的掃描式電子顯微鏡(SEM)照片 61
 5.7.5釋放過後單獨微粒的掃描式電子顯微鏡(SEM)照片 62
 5.7.6蠶絲蛋白/明膠薄膜經水降解後表面形態 64
 5.7.7蠶絲蛋白/明膠薄膜包覆微粒表面形態 65
第六章 結論 70
參考文獻 71



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