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

吳政隆

指導教授 ： 陳家俊

國立臺灣師範大學/理學院/化學系/碩士(2007年)

摘要

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。

關鍵字

氧化鋅奈米粒子 ； 雙光子顯微術 ； 皮膚滲透

並列摘要

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.

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