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研究生: 吳政隆
論文名稱: 利用雙光子顯微術觀察與量化化學增益劑誘使變化在氧化鋅奈米粒子經皮傳輸上
Visualization and Quantification of Chemical Enhancers Induced Changes in Transdermal Zinc Oxide Nanoparticles Transport Using Two-Photon Microscopy
指導教授: 陳家俊
Chen, Chia-Chun
學位類別: 碩士
Master
系所名稱: 化學系
Department of Chemistry
論文出版年: 2008
畢業學年度: 96
語文別: 中文
中文關鍵詞: 氧化鋅奈米粒子雙光子顯微術皮膚滲透
論文種類: 學術論文
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  • 本篇文章目的在於利用雙光子顯微術(TPM)來探討氧化鋅奈米粒子(ZnO NPs)在皮膚上能夠滲透多少以及量化ZnO NPs利用化學增益劑時(如油酸(OA)與乙醇)的滲透增益效應。能夠描述及了解使用了化學增益劑的ZnO NPs在滲透角質層(SC)的經皮傳輸上,能夠用助於設計防曬品的模式。
    TPM為一種非侵入性的方式可用在活體上或活體外人類的皮膚的成像,能直接顯現皮膚結構特徵。有研究指出ZnO具有二階非線性光學係數,觀察到ZnO具有二倍頻訊號(SHG)。利用TPM結合裸鼠皮自發螢光以及ZnO的SHG訊號,能夠用來觀察滲透的路徑與測量ZnO使用與未使用化學性增益劑在SC所滲透的深度。由於化學性增益劑的使用誘使改變ZnO NPs在經皮傳輸的一些性質,包含vehicle to the skin partition coefficient (K), the SHG intensity gradient (dI/dz) and the effective diffusion path length (l),這些將透過三維影像處理來進行理論的分析,評估在裸鼠皮上的效應。
    本實驗中,結果指出(1)ZnO加入與未加入增益劑的滲透深度分別為少於40μm與20μm。(2)ZnO沿角質間隙滲透,最後到達較上層的活化表皮層,而沒有到真皮層。(3)關於傳輸性質的增益值能幫助我們了解增益劑是否有效。

    The aim of this research is using two-photon microscopy (TPM) to visualize how much the skin depth of the zinc oxide nanoparticles (ZnO NPs) penetrating and to quantify the penetration enhancing effect of the ZnO NPs with chemical enhancers (such as Oleic acid - OA and ethanol). A description and understanding of the penetration into the stratum corneum (SC) involved in chemically enhanced transdermal ZnO NPs transport can be used for the design of sunscreen formulations.
    TPM has been used to image in vivo and in vitro human skin as a noninvasive method for directly visualizing the skin structural features. Second-order nonlinear coefficient of ZnO NPs were characterized, and second harmonic generation (SHG) was observed from ZnO NPs. The combination of the autofluorescence of nude mouse skin and the SHG of ZnO NPs has been used to image and measure the penetration pathway and depth of ZnO NPs treated with and without chemical enhancers into the SC. The changes induced by chemical enhancers in the transport properties of the ZnO NPs, including the vehicle to the skin partition coefficient (K), the SHG intensity gradient (dI/dz) and the effective diffusion path length (l), were quantified relative to the control case (without enhancers) utilizing a theoretical analysis of the three-dimensional images for evaluating the effects on nude mouse skin.
    In this work, the results demonstrate that (1) the skin depths of ZnO NPs with and without chemical enhancers penetrating are less than 40μm and 20μm, respectively, (2) ZnO NPs penetrate beyond SC and into the upper viable epidermis, not into the dermis. (3) The enhancements of the transport property are available to understand whether the enhancers induced changes in SC.

    總目錄…………………………………………………………………Ⅰ 中文摘要………………………………………………………………Ⅳ 英文摘要………………………………………………………………Ⅴ 圖目錄…………………………………………………………………Ⅵ 表目錄…………………………………………………………………Ⅷ 第一章 緒論……………………………………………………………1 1-1 引言……………………………………………………………1 1-2 紫外線的傷害…………………………………………………3 1-3 皮膚結構簡介…………………………………………………5 1-3-1 經皮吸收……………………………………………………7 1-3-2 促進劑………………………………………………………7 1-4 防曬品簡介……………………………………………………10 1-5 氧化鋅(ZnO)…………………………………………………12 1-5-1 ZnO發光機制………………………………………………13 1-5-2 ZnO非線性光學性質………………………………………14 1-5-3 奈米ZnO製備方法與機制…………………………………14 1-6 增益劑誘使改變之相關增益係數……………………………18 第二章 實驗……………………………………………………………22 2-1 研究動機與目的………………………………………………22 2-2 奈米ZnO之合成………………………………………………23 2-2-1 合成ZnO nanoparticles與nanorods所需藥品……………23 2-2-2 測量儀器……………………………………………………23 2-2-3 合成ZnO nanoparticles…………………………………… 23 2-2-4 合成ZnO nanorods…………………………………………25 2-2-5 ZnO的octanol-PBS partition coefficient(KO/PBS)測試…… 26 2-2-6 ZnO donor solution配置…………………………………… 27 2-3 皮膚樣品製作…………………………………………………28 2-4 雙光子顯微鏡簡介……………………………………………29 2-5 雙光子顯微鏡儀器與設備……………………………………31 第三章 結果與討論……………………………………………………34 3-1 合成之ZnO材料性質…………………………………………34 3-2 使用雙光子顯微鏡觀察ZnO經皮滲透之影像分析…………38 3-2-1 ZnO的空白測試…………………………………………… 38 3-2-2 ZnO octanol-PBS partition coefficient(KO/PBS)…………… 39 3-2-3 ZnO nanostructures經皮滲透的影像……………………41 3-2-4 ZnO nanoparticles經皮滲透的影像分析…………………43 3-3量化增益劑誘使改變在經皮傳輸ZnO NPs上之增益值………51 第四章 結論與未來展望………………………………………………56 參考文獻………………………………………………………………58

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