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研究生:王德華
研究生(外文):Tak‐Wah Wong
論文名稱:以無痛電穿孔促進藥物之經皮吸收
論文名稱(外文):Enhancing transdermal drug delivery with painless electroporation
指導教授:李玉雲李玉雲引用關係呂增宏
指導教授(外文):Yu-Yun LeeTzeng-Horng Leu
學位類別:博士
校院名稱:國立成功大學
系所名稱:臨床醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:英文
論文頁數:153
中文關鍵詞:無痛經皮藥物吸收滅可善糖尿病胰島素電穿孔
外文關鍵詞:methotrexatediabetespainlessElectroporationtransdermal drug deliveryinsulin
相關次數:
  • 被引用被引用:1
  • 點閱點閱:206
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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
藥物經皮吸收比其他路徑投藥的優點包括簡易、方便、安全及
局部藥物濃度高,2007 年美國相關於經皮藥物吸收市場達到16.3 百萬美元,其重要性可見一斑。然而,皮膚的天然屏障讓許多大分子藥物包括荷爾蒙、DNA 疫苗及RNAi 等無法通過。
以電穿孔促進藥物經皮吸收開啟了克服皮膚屏障的一個新方
向,但是,在電穿孔時所產生的疼痛使大部分病人無法接受此種治療方法。在本篇論文中,我們首先證實抗癌藥物-滅可善(methrotrexate,454 Da)在稍微提高皮膚溫度的條件下施行電穿孔,可以在猪皮膚上達到治療目的之藥物濃度。為了達到無痛電穿孔的目的,我們發明了一個微陣列電穿孔電極。在人類皮膚無痛的電穿孔條件下,滅可善可以成功的進入老鼠皮膚,最後,我們首次將具有大分子量的胰島素(5.8kDa),經由相同電穿孔條件,成功的進入老鼠體內,這些結果顯示未來無痛電穿孔經皮傳遞大分子藥物,包括胰島素之可能性。
Transdermal drug delivery has the advantages of simplicity, convenience, safe and higher local concentration compared to other routes of drug administration. The market of transdermal drug delivery reaches US$16.3 million in 2007. Nevertheless, skin barrier prevents large molecules such as peptide hormones and vaccines as well as minigenes and RNAi etc. through the transdermal route.
The application of electroporation to enhance transdermal drug delivery has opened up a new possibility to break through skin barrier. However, the intolerable
pain during electroporation makes this therapy unacceptable to most patients. In this thesis, we first proved that therapeutic level of anticancer drug- methotrexate (molecular weight of 454 Da) could be transdermal delivered into porcine skin with electroporation under mild hyperthermia. We then invented a needle-free microelectrode array for the purpose of painless electroporation. Under conditions of creating effective electropores on human skin painlessly, methotrexate was successfully delivered into mouse skin. Finally, we showed for the first time, the success of transderaml delivery of insulin (5.8 KDa) to mice using this new electrodes array with an electroporation condition that is painless to human. The results suggested painless delivery of large molecule including insulin through human skin is possible in future clinical practice.
Contents
English abstract 1
Chinese abstract 2
Acknowledgement 3
Abbreviations 8
Figures content 9
Chapter 1.
Introduction 10
1.1 Background 11
1.2 Hypothesis and aims 17
1.3 Figures 18
Chapter 2. Pilot study of topical delivery of methotrexate by
electroporation 26
2.1 Introduction 27
2.2 Material and methods 29
2.3 Results and Discussions 33
2.4 Figure Legends 42
2.5 Figures 43
Chapter 3. Painless electroporation with a new needle-free
microelectrode array to enhance transdermal drug
delivery 46
3.1 Introduction 47
3.2 Material and Methods 47
3.3 Results and Discussions 51
3.4 Figure Legends 57
3.5Figures 59
Chapter 4. Enhancing transdermal delivery of insulin with
painless electroporation 67
4.1 Introduction 68
7
4.2 Material and Methods 70
4.3 Results and Discussions 77
4.4 Figure Legends 88
4.5 Figures 91
Chapter 5. Summary and Future Prospect 97
5.1 Summary 98
5.2 Future prospect 98
5.3 Figures 100
References 102
Appendix 111
Author’s biography 138
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