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研究生: 陳兆廷
Chao-Ting Chen
論文名稱: 探討聚己內酯薄膜降解情形以及Ketoprofen 與Silver-sulfadiazine之藥物釋放實驗
In vitro Degradation of Polycaprolactone Thin films and In vitro Release of Ketoprofen and Silver-sulfadiazine
指導教授: 王孟菊
Meng-Jiy Wang
口試委員: 李澤民
Tzer-Min Lee
蔡偉博
Wei-Bor Tsai
林睿哲
Jui-Che Lin
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: 2011
畢業學年度: 99
語文別: 中文
論文頁數: 93
中文關鍵詞: 聚己內酯藥物釋放ketoprofensilver-sulfadiazine電漿改質Franz diffusion cellMTTLDH
外文關鍵詞: Polycaprolactone, drug release, ketoprofen, silver-sulfadiazine, plasma modification, Franz diffusion cell, MTT, LDH
相關次數: 點閱:195下載:3
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  • 本研究是利用聚己內酯 (polycaprolactone, PCL)當做基材,以聚乙二醇 (polyethylene glycol, PEG)做為造孔劑,並使用濕式相分離法製備出不含孔洞結構的PCL薄膜、以及含微孔洞結構的PCL-PEG薄膜。並進行兩個部份的實驗,分別為降解試驗以及藥物釋放試驗。首先,降解試驗是藉著浸泡於pH值7.4的PBS溶液並置於37℃的烘箱中,進行為期五個月的降解試驗,從重量損失分析、分子量變化、表面型態、以及機械強度中,觀察並分析降解五個月PCL與PCL-PEG薄膜的物化性質。
    利用Franz diffusion cell進行藥物釋放的試驗,把含有微孔洞結構的PCL-PEG薄膜,利用不同電漿改質改變其表面性質,比較ketoprofen與silver-sulfadiazine兩種不同藥物釋放的速率。本研究也使用親水性高的奈米細菌纖維素膜為基材進行藥物釋放的研究。在經過為期14天的藥物釋放週期,由結果可發現,對於ketoprofen而言,未改質的PCL-PEG薄膜擁有較高的平均累積釋放率,然而經過CF4電漿改質後的PCL-PEG薄膜,卻有較低的平均累積釋放率;對於silver-sulfadiazine而言,不論是未改質的PCL-PEG薄膜或細菌纖維素膜、以及經過電漿改質的PCL-PEG薄膜,皆有相似的累積釋放率。為了確認PCL-PEG薄膜的生物相容性,利用LDH以及MTT實驗,培養L-929細胞,比較經ketoprofen與silver-sulfadiazine兩種藥物對於細胞的毒性測試,分成直接加藥予細胞吸收以及逐漸釋放使細胞吸收兩種方法,結果發現,兩種藥物對於L-929細胞皆有毒性反應,與不含藥的條件相比,細胞活性有統計學上的明顯差異。


    Polycaprolactone is a hydrophobic, semi-crystalline biodegradable polymer with a relatively slow degradation rate. In this study, the in-vitro degradation of polycaprolactone (PCL) and porous PCL, generated by mixing polyethylene glycol with PCL (PCL-PEG) during the membrane formation process, were investigated by weight loss percentage, variation of molecular weight, surface morphology and mechanical strength for 5 months.
    Moreover, a control release system composed of surface modified porous PCL membranes combined with a layer sol-gel was reported. The drugs chosen for control-release experiments were silver-sulfadiazine (AgSD) and ketoprofen which were impregnated in the sol-gel. The surface modification was achieved by oxygen (O2) and tetrafluorocarbon (CF4) plasmas. The pristine and plasma-treated surfaces were characterized by water contact angle measurement, atomic force microscope (AFM), scanning electron microscope and electron spectroscopy for chemical analysis (ESCA). The results showed that the release rate of silver-sulfadiazine was similar on pristine PCL. It was noted that the plasma-treated porous PCL membrane exhibited a slower release rate. On the other hand, the release rate of ketoprofen revealed no significant difference on PCL and plasma modified membranes. Furthermore, the interactions between drugs and mammalian cells were examined by using MTT assays to evaluate the toxicity. The cell viability was about 97% and 90% for 1 day and 5 days release period for AgSD and ketoprofen, respectively.

    摘要 I Abstract II 致謝 III 圖目錄 VII 表目錄 X 公式目錄 XI 第一章 緒論 1 1-1 前言 1 1-2 研究目的與動機 1 第二章 文獻回顧 3 2-1 可降解性高分子 3 2-1-1 生物可降解性高分子種類 3 2-2 聚己內酯 (polycaprolactone, PCL) 4 2-3 藥物傳遞應用 5 2-3-1 體外擴散實驗方法:Franz diffusion cell 6 2-3-2 Franz diffusion cell實驗 6 2-3-3 藥物偵測法 8 2-4 傷口 9 2-4-1 傷口復原 9 2-4-2 傷口敷料 10 2-5 表面改質 12 2-6 細菌纖維素膜 (bacterial cellulose, BC) 12 2-7 甲殼素 (chitosan) 13 2-8 水膠 (sol-gel) 13 2-9 包埋藥物 14 2-9-1 酮基布洛芬 (ketoprofen) 14 2-9-2 銀磺胺嘧啶 (Silver-sulfadiazine, AgSD) 15 第三章 實驗材料與方法 16 3-1 Materials 16 3-1-1 Bacterial cellulose 16 3-1-2 Chemical for preparimg PCL-PEG membrane 16 3-2 Chemicals 16 3-2-1 Chemicals for sol-gel preparations 16 3-2-2 Cell culture 17 3-2-3 MTT assay 17 3-2-4 LDH assay 18 3-3 Equipment and instruments 18 3-4 Experimental procedures 19 3-4-1 Preparation of PCL-PEG membrane 19 3-4-2 Preparation of sol-gel 20 3-4-3 Plasma treatments on PCL-PEG 20 3-4-4 Drug release analyses by using Franz diffusion cells 21 3-4-5 Preparation of cell culture medium 22 3-4-6 Preparation of MTT solution 22 3-4-7 Cell culture procedure 22 3-4-8 Cell viability (MTT assay) 24 3-5 Surface characterizations 24 3-5-1 Water contact angle (WCA) 24 3-5-2 Fourier Transform Infrared- Attenuated Total Reflectance (FTIR-ATR) 25 3-5-3 Gel permeation chromatograph (GPC) 25 3-5-4 Electron spectroscopy for chemical analysis (ESCA) 25 3-6 Statistical analysis 26 第四章 結果與討論:降解分析 27 4-1 重量變化分析 27 4-2 表面型態分析 28 4-3 薄膜的孔洞分析 29 4-4 分子量的變化 30 4-5 機械強度 30 第五章 結果與討論:藥物釋放 58 5-1 細菌纖維素膜特性 58 5-2 PCL-PEG薄膜的表面特性 58 5-2-1 水接觸角 (Water contact angle) 58 5-2-2 表面型態 (SEM) 59 5-2-3 表面官能基鑑定 (ATR-FTIR) 59 5-2-4 表面化學組成分析 (ESCA) 60 5-3 模擬體外藥物釋放試驗 61 5-3-1 利用全波長掃描檢測ketoprofen和silver-sulfadiazine 61 5-3-2 藥物釋放量的計算 61 5-3-3 Ketoprofen 釋放試驗 62 5-3-4 Silver-sulfadiazine 釋放試驗 64 5-4 細胞行為 65 5-4-1 LDH分析 65 5-4-2 MTT測試 66 第六章 結論與未來展望 77 6-1 PCL與PCL-PEG降解試驗 77 6-2 藥物釋放結果 77 6-3 未來展望 78

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