董成淵臺灣大學：物理研究所孫嬿Sun, YenYenSun2007-11-262018-06-282007-11-262018-06-282004http://ntur.lib.ntu.edu.tw//handle/246246/54562通過皮膚藥物的傳遞(transdermal drug delivery)是利用物理及化學方法將藥物傳送通過皮膚的一種機制，它具有諸多優點包含了可維持血液中藥物濃度的穩定、無痛、及方便性。然而，有效的將藥物傳遞通過皮膚卻十分困難，因為角質層扮演一個阻擋外來物如藥物進入的屏障，有釵h研究針對利用各種物理及化學機制增加藥物傳遞的速率，如化學增進劑、微小電流、以及大電流、光—力學波以及超音波，然而這些方法的作用機制仍然沒有全然的被了解。這個實驗中我們應用雙光子偏振及廣意義偏振影像來了解人類皮膚角質層以及真皮纖維的結構，我們發現雙光子偏振影像是一個很好的方法來研究皮膚結構的排列，而廣義偏振則可用於了解皮膚的微觀化學環境，我們證明結合偏振及廣義偏振影像可以了解油酸於通過皮膚藥物的傳遞的作用機制，我們的結果說明結合偏振及廣義偏振影像可使我們監控生物結構中物理及化學環境的變化。Transdermal drug delivery utilizes physical or chemical techniques to transport drugs across the skin. This approach has many advantages including being able to maintain a steady drug concentration in vivo, painless, and convenient. However, to efficiently delivery effective dosage of therapeutic through the skin is difficult due to the presence of the stratum corneum as the main barrier to the ingress of exogenous materials, such as therapeutic drugs. Many investigations have been performed to improve drug permeation across the skin using chemical or physical enhancement techniques: application of chemical enhancers, iontophoresis, electroporation, photomechanical wave and sonophoresis . However, the mechanisms of these techniques are not perfectly understood. In this work we demonstrate the application of multiphoton polarization and generalized polarization imaging in resolving the structures in surface stratum corneum and dermal layers in ex-vivo human skin. We found that multiphoton polarization imaging can be a powerful method in identifying structural orientations in the skin. On the other hand, multiphoton generalized polarization imaging is useful in revealing the microscopic chemical environment of the skin. We demonstrate that by combing mutiphoton polarization imaging and generalized polarization imaging, we can gain insight into the mechanism of the oleic acid enhanced transdermal drug delivery. Our results show that combined polarization and GP microscopy can be used to characterize the physical and chemical changes in biological structures.英文摘要 1 中文摘要 2 第一章 緒言 1.1研究動機及目標 3 1.2非線性顯微術顯微術發展的歷史及其應用發展 6 第二章 實驗原理及方法 2.1雙光子顯微鏡的基本原理 9 2.2雙光子顯微系統的架設 20 2.3染劑的介紹：Laurdan 25 2.4皮膚構造 32 2.5樣品製作 36 2.6光路上的調整與物鏡的選擇 38 2.7針對偏振所做的矯正 40 2.8 Saturation測試 46 第三章 實驗結果與討論 3.1皮膚角質層及真皮纖維的偏振特性實驗結果及討論 48 3.2由皮膚偏振及廣義偏振影像觀測油酸的做作 用機制之實驗結果及討論 54 第四章 結論 4.1結論 64 參考資料 662066639 bytesapplication/pdfen-US雙光子顯微術皮膚藥物傳遞transdermal drug deliverytwo photon microscopythesishttp://ntur.lib.ntu.edu.tw/bitstream/246246/54562/1/ntu-93-R91222012-1.pdf