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研究生: 紅忠緯
Chung-Wei Hung
論文名稱: 製備聚乙烯醇/氧化石墨烯複合材料並應用於藥物擴散控制
The modulation of drug release rate of ketoprofen by using thin film composites
指導教授: 王孟菊
Meng-Jiy Wang
口試委員: 葉昀昇
Yun-Sheng Ye
李振綱
Cheng-Kang Lee
周秀慧
Shiu-Huey Chou
學位類別: 碩士
Master
系所名稱: 工程學院 - 化學工程系
Department of Chemical Engineering
論文出版年: 2012
畢業學年度: 100
語文別: 中文
論文頁數: 67
中文關鍵詞: 聚乙烯醇氧化石墨烯藥物釋放傷口癒合
外文關鍵詞: poly(vinyl alcohol), graphene oxide, drug release, wound healing
相關次數: 點閱:313下載:14
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  本研究使用非類固醇抗發炎藥物酮基布洛芬 (ketoprofen) 作為測試藥物,以羧甲基纖維素 (carboxymethyl cellulose, CMC) 作為乘載藥物的薄膜,並藉由混摻不同比例的氧化石墨烯 (graphene oxide, GO) 於聚乙烯醇 (poly(vinyl alcohol), PVA) 薄膜中,增加複合材料結構上的立體障礙,以控制藥物釋放的速率,而所製備的複合材料具有良好的吸水能力,可以維持傷口濕潤的環境,促進細胞的遷移及增生,本論文以體外的細胞測試評估作為傷口敷料之可行性後,選出適當的組別進行傷口敷料之活體動物實驗,觀察其應用於開放性傷口上之特性。
  以掃描式電子顯微鏡 (scanning electron microscopy, SEM) 觀察複合材料的截面結構,結果顯示截面出現不規則的皺摺,可得知氧化石墨烯均勻分散於聚乙烯醇結構中。以Franz diffusion cell進行藥物釋放試驗,為期24小時的藥物釋放週期,結果顯示,未使用薄膜進行不同藥物濃度的釋放試驗,t50 (time taken to release 50 % of the drug) 的平均值約為0.9小時,而混摻1、3及5 wt.%的氧化石墨烯於聚乙烯醇中,t50分別為2.8、6.7及14.9小時,顯示藥物釋放的速率可藉由複合薄膜成分進行調控。在細胞培養測試方面,經由MTT assay分析結果得知,不同混摻條件的薄膜對於老鼠纖維母細胞 (L-929 fibroblasts),均無明顯的細胞毒性,而LDH assay結果顯示,氧化石墨烯含量增加使得細胞容易貼附及增生於材料表面,證實複合材料具有良好的生物相容性。
  以上實驗結果顯示,本研究製備之複合材料,除了能減緩藥物釋放的速率,還具有良好的生物相容性, 並且能維持傷口環境的濕潤,具有應用於傷口敷料的潛力。


In this work, the drug release system is adopted to incorporate ketoprofen in carboxymethyl cellulose (CMC) matrix to prepare thin film for drug delivery. The aim of this study is to control the drug diffusion rate by controlling the amount of graphene oxide (GO) in poly(vinyl alcohol) (PVA) to form PVA/GO composites. To assay the biocompatibility of PVA/GO composites, cellular behavior on the membranes was analyzed using LDH assay and MTT assay to observe the results of cell proliferation and adhesion. Finally, in vivo animal experiments using PVA/GO composite were performed on mice to investigate the effects on the wound healing.
Scanning electron microscope (SEM) graphs showed that the cross-sections of the composites present an irregular surface after blending with GO. In vitro release experiments using composites showed that the increase of the concentration of GO in PVA can delay the drug diffusion rate. When seeding the cells (L-929 fibroblasts) on the PVA/GO composites, in vitro LDH and MTT assay results indicated that the composites have excellent biocompatibility.
These results showed that the PVA/GO composites can reduce the drug release rate and showed good biocompatibility. The composites maintained a moist environment with the potential application to the wound dressing.

摘要 i Abstract ii 致謝 iii 總目錄 iv 圖目錄 vii 表目錄 ix 第一章 緒論 1 1.1 研究背景 1 1.2 研究目標 2 第二章 文獻回顧 3 2.1 傷口介紹 3 2.2 傷口癒合 3 2.3 傷口敷料 5 2.4 傷口敷料的種類 6 2.5 藥物傳遞 9 2.6 聚乙烯醇 11 2.7 氧化石墨烯 13 2.8 羧甲基纖維素 14 2.9 Franz diffusion cell 15 2.10 Ketoprofen 16 第三章 實驗材料與方法 18 3.1 實驗藥品 18 3.2 實驗儀器 18 3.3 實驗方法 19 3.3.1 氧化石墨烯的製備 19 3.3.2 聚乙烯醇/氧化石墨烯複合材料的製備 20 3.3.3 羧甲基纖維素/ketoprofen薄膜的製備 20 3.4 實驗設備與器材 21 3.4.1 傅立葉轉換紅外光譜儀 21 3.4.2 掃描式電子顯微鏡 21 3.4.3 X光射線繞射分析 22 3.4.4 電子能譜化學分析儀 22 3.4.5 熱重量分析法 23 3.4.6 示差掃描熱分析 23 3.4.7 含水率測試 24 3.4.8 通透性測試 24 3.4.9 藥物釋放實驗 25 3.4.10 細胞貼附行為測定 (LDH assay) 26 3.4.11 細胞存活率測定 (MTT assay) 26 3.4.12 統計學分析 (statistical analysis) 27 第四章 結果與討論 28 4.1 GO之型態分析 28 4.2 複合材料之型態觀察 29 4.3 PVA、GO及PVA/GO複合材料之官能基鑑定 31 4.4 薄膜材料熱性質分析 32 4.5 PVA、GO及PVA/GO複合材料之X光射線繞射分析 35 4.6 吸水性測試 36 4.7 不同比例的GO混摻於PVA之ketoprofen的通透性測試 38 4.8 體外藥物釋放的測試 40 4.9 表面元素含量之ESCA分析結果 44 4.10 不同比例條件PVA/GO複合材料之細胞適應性評估 47 4.11 傷口癒合之動物實驗 51 第五章 結論 54 第六章 參考文獻 56 問題與建議 63

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