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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 董成淵 | |
dc.contributor.author | Chiu-Sheng Yang | en |
dc.contributor.author | 楊秋晟 | zh_TW |
dc.date.accessioned | 2021-06-16T13:01:24Z | - |
dc.date.available | 2023-12-20 | |
dc.date.copyright | 2013-08-09 | |
dc.date.issued | 2013 | |
dc.date.submitted | 2013-08-07 | |
dc.identifier.citation | 參考資料
1. Hsu, H.-C., Two-Photon Visualization of Transport Dynamics in Oleic Acid-Induced Transdermal Delivery. Master thesis, 2010. 2. Prausnitz, M.R. and R. Langer, Transdermal drug delivery. Nature Biotechnology, 2008. 26(11): p. 1261-1268. 3. Ball, A.M. and K.M. Smith, Optimizing transdermal drug therapy. American Journal of Health-System Pharmacy, 2008. 65(14): p. 1337-1346. 4. Pirot, F., et al., Characterization of the permeability barrier of human skin in vivo. Proceedings of the National Academy of Sciences of the United States of America, 1997. 94(4): p. 1562-1567. 5. Wertz, P.W., et al., Essential fatty acids and epidermal integrity. Archives of Dermatology, 1987. 123(10): p. 1381-1384. 6. Williams, M.L. and P.M. Elias, The extracellular matrix of stratum corneum: Role of lipids in normal and pathological function. Critical Reviews in Therapeutic Drug Carrier Systems, 1987. 3(2): p. 95-122. 7. Moser, K., et al., Passive skin penetration enhancement and its quantification in vitro. European Journal of Pharmaceutics and Biopharmaceutics, 2001. 52(2): p. 103-112. 8. Golden, G.M., J.E. McKie, and R.O. Potts, Role of stratum corneum lipid fluidity in transdermal drug flux. Journal of Pharmaceutical Sciences, 1987. 76(1): p. 25-28. 9. Ongpipattanakul, B., et al., Evidence that oleic acid exists in a separate phase within stratum corneum lipids. Pharmaceutical Research, 1991. 8(3): p. 350-354. 10. Francoeur, M.L., G.M. Golden, and R.O. Potts, Oleic acid: Its effects on stratum corneum in relation to (trans)dermal drug delivery. Pharmaceutical Research, 1990. 7(6): p. 621-627. 11. Anissimov, Y.G., et al., Mathematical and pharmacokinetic modelling of epidermal and dermal transport processes. Advanced Drug Delivery Reviews, 2013. 65(2): p. 169-190. 12. Rim, J.E., P.M. Pinsky, and W.W. van Osdol, Using the method of homogenization to calculate the effective diffusivity of the stratum corneum with permeable corneocytes. Journal of Biomechanics, 2008. 41(4): p. 788-796. 13. 王俊欽, Utilizing nonlinear optical microscopy to diagnose human bladder tumor and the development of early cancer imaging techniques in nude mice in vivo. Master thesis. 2005. 14. Wolf, M.B.E., Principles of Optics: Electromagnetic Theory of Propagation, Interference and Diffraction of Light Pergamon. 15. Yu, B., et al., In vitro visualization and quantification of oleic acid induced changes in transdermal transport using two-photon fluorescence microscopy. Journal of Investigative Dermatology, 2001. 117(1): p. 16-25. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/61347 | - |
dc.description.abstract | 常見的藥物治療方式有三種,分別是口服、注射以及經皮傳輸治療,由於口服及注射有一些缺點在,而經皮傳輸治療有其特有的優點,主要就是藥物藉由皮膚的滲透,然後使藥物進入到人體的微血管並再達到人體循環系統來達到治療的目的,而我的研究主要就是利用雙光子顯微術來研究觀察藥物在皮膚表皮上滲透,並算出擴散係數,來理解分子在皮膚表面滲透的情形。
我們所使用的螢光分子主要是SRB (Sulforhodamine B) 及RBHE (Rhodamine B Hexyl Ester),SRB是一種親水性分子而RBHE是恐水性分子,這兩種分子在結構及光譜方面非常相似,所以我們選擇這兩種分子來做比較。並用雙光子顯微鏡觀察滲透的動態過程。我們將這兩種分子分別與酒精及磷酸鹽緩衝溶液做混合,此外我們將實驗分為控制組及額外添加3% v/v油酸的實驗組,因為油酸本身有改善皮膚滲透的能力,所以我們要比較含油酸跟沒含油酸的實驗結果差異。而我們發現不論是隨著SRB、RBHE滲透路徑主要都是藉由細胞與細胞的間隙,但是在細胞內RBHE的滲透能力優於SRB,而油酸的加入,增強了分子滲透的能力,但是同時也增加了皮膚的異質性,使得角質細胞形狀明顯的改變。 此外,現今有很多近似角質層結構的模型,理想均質膜的模型就是其中一種,我們將角質層假設成一個均質膜,藉由Fick’s Law和連續方程,得到一個擴散方程,再藉由邊界條件可以得到一個濃度與時間和位置有關的擴散方程解,方程式裡面有個係數叫擴散係數,而我們想要得到SRB、RBHE在皮膚角質上擴散係數的值,我們用Matlab跟Labview去做結合,針對影像每個像素(pixel)去做擬合,我們在同個深度7個時間點擬合出擴散係數,而我們得到了擴散係數分布圖,並得知無論是SRB還是RBHE,細胞與細胞間隙的擴散係數是大於細胞內的,並針對單一角質細胞去看擴散係數在細胞間隙與細胞內隨著深度的差異,而結果顯示不論是細胞內還是細胞間隙,SRB和RBHE的擴散係數都隨著深度逐漸下降。 | zh_TW |
dc.description.abstract | Currently there are three commonly applied methods for drug delivery including oral delivery, hypodermic injection and transdermal methodologies. Unfortunately, there are some disadvantages associated with oral delivery and hypodermic injection, therefore, in this research we focused on transdermal drug delivery system that has a handful of merits over conventional methods. The drug can diffuse into the deeper subcutaneous depth in the skin tissue by the process of permeation, reach the blood capillary, and finally enter the circulatory system for the therapeutic treatment. We utilized two-photon fluorescence microscopy to study the drug permeation on stratum corneum (SC) in order to calculate the diffusion coefficient and understand the detailed permeation process in skin specimens.
The two fluorescent probes including SRB (Sulforhodamine B) and RBHE (rhodamine B hexyl ester) were served as the modeling of hydrophobic and hydrophilic drug agents, respectively, and were selected based on their similarity in molecular structure, and fluorescence emission range. These two fluorescent probes were used for the purpose of comparison and were applied in the following manner. We first mixed SRB with ethanol as well as with PBS as the control group combination. Secondly, we mixed RBHE, separately, with ethanol, PBS, and 3% v/v oleic acid, and used these combinations as the experimental group. Due to the fact that oleic acid can enhance the ability of drug permeation in skin, we compared the results with and without oleic acid. Our analytic results suggested that both SRB and RBHE reached the deeper subcutaneous layer via intercellular route. In addition we discovered that the ability of permeation of RBHE in intracellular area is better than that of SRB. The addition of oleic acid not only enhances the molecule’s permeative ability but also increase its heterogeneity and the revelation of the shape of the cell. Furthermore, there are several models illustrating the physical structure of stratum corenum. In our theoretical modeling we treated stratum corenum as a homogeneous membrane. By Fick’s law and the continuous equation we can obtain a differential diffusion equation. There is a unique diffusion coefficient associated with the diffusion equation for both the permeation of SRB and RBHE in the stratum corenum of skin. For both the permeation of SRB and RBHE we combined the Matlab with Labview, analyzed every pixel of images, fitted the diffusion equation, and obtained the diffusion coefficient from the same depth at seven different time points. Finally, we obtained the distribution diagram and recognized that the value of diffusion coefficient in intercellular domain is higher than that in the intracellular region for both SRB and RBHE. The difference of diffusion coefficients between intracellular and intercellular area were observed at different depths for particular type of cells in stratum corenum, and the results showed that the diffusion coefficients for SRB and RBHE decrease with the increasing depth both intracellular and intercellular regions. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T13:01:24Z (GMT). No. of bitstreams: 1 ntu-102-R00245007-1.pdf: 1781195 bytes, checksum: ccabcbe6d925caac32c9be8e40155704 (MD5) Previous issue date: 2013 | en |
dc.description.tableofcontents | 目錄
第1章 藥物經皮傳遞簡介 1 1.1發展背景與研究動機 1 1.2 皮膚的結構 2 1.3 藥物傳遞經皮傳遞所面臨到的阻礙---角質層 3 第2章 物質的擴散 5 2.1 研究的歷史背景 5 2.2 菲克定律(Fick’s Law) 6 2.2.1菲克第一定律(Fick’s First Law) 6 2.2.2連續方程(The continuity Equation) 7 2.2.3菲克第二定律(Fick’s Second Law)---擴散方程 8 2.3 與時間無關的擴散過程 9 2.3.1平衡態的擴散過程 9 2.3.2穩定態的擴散過程 9 2.4粒子在均質膜中的擴散情況 11 2.4.1在均質膜中穩定態的擴散 11 2.4.2擴散方程的解(在均質模中) 12 2.4.3 擴散方程通解與實驗的結合 16 第3章 多光子顯微術的原理 18 3.1多光子光學顯微術發展的歷史 18 3.2 雙光子理論 19 3.2.1雙光子與單光子的比較 19 3.2.2雙光子原理的數學推導: 20 3.3 點括函數與數值孔徑 26 3.3.1 Huygens-Fresnel原理 26 3.3.2 點擴函數 27 3.3.3 數值孔徑與解析度 31 第4章 實驗步驟及方法 35 4.1 螢光分子 35 4.2雙光子顯微鏡系統及實驗光學元件 36 4.3實驗流程 38 第5章 實驗結果與分析討論 41 5.1 SRB 控制組與實驗組 43 5.2 RBHE控制組與實驗組 47 5.3 擴散係數分布 52 5.3.1 SRB擴散係數分布 53 5.3.2 RBHE擴散係數分布 55 第6章 結論 57 | |
dc.language.iso | zh-TW | |
dc.title | 利用雙光子螢光顯微術觀察分子在角質層上滲透情形 | zh_TW |
dc.title | Observation of molecular permeation through the stratum corneum by multiphoton fluorescence microscopy | en |
dc.type | Thesis | |
dc.date.schoolyear | 101-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳永芳,張顏暉,石明豐 | |
dc.subject.keyword | SRB,RBHE,雙光子螢光顯微術,擴散係數,角質層,親水性分子,恐水性分子, | zh_TW |
dc.subject.keyword | diffusion,coefficients,stratum corenum,SRB,RBHE,two-photon excitation fluorescence microscopy,hydrophobic molecule,hydrophilic molecule, | en |
dc.relation.page | 59 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2013-08-07 | |
dc.contributor.author-college | 理學院 | zh_TW |
dc.contributor.author-dept | 應用物理所 | zh_TW |
顯示於系所單位: | 應用物理研究所 |
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