臺灣博碩士論文加值系統

本研究使用穿透式電子顯微鏡(Transmission electron microscope, TEM)、動態光散射粒徑分析儀(Dynamic Light Scattering, DLS)、螢光光譜儀 (Fluorescence Spectroscopy, FL)以及微分式掃描熱卡計(Differential Scanning Calorimetry, DSC)來探討Compound T (T)及乙醇含量對V(V)奈米聚集體物理性質的影響。且藉由Franz擴散槽進行體外滲透效能評估。此外，在25℃下，使用技術與螢光顯微鏡，探討氣/液界面上混合V/T單分子層行為與觀察單分子層型態變化。結果顯示，隨T含量增加V奈米聚集體粒徑下降、界面電位上升，且改變型態。添加T會使V聚集體膜呈現多重相態，隨著T含量增加膜主相變溫度下降轉為更鬆散的相態。在25℃下，添加少量T能使脂雙層疏水及親水頭基區域分子流動性下降。T的添加使緊密的V單分子層轉變為較鬆散的單分子層，並可壓縮至更高表面壓。混合V/T 8/2單分子層具有熱力學上的最佳穩定性。乙醇濃度2-20% (v/v)範圍內，隨乙醇含量增加使聚集體粒徑先下降後上升、界面電位越趨電中性。混合V/T的主相變溫度隨乙醇含量增加而下降，使分子間作用力降低排列更凌亂。在含有T的組成中，當乙醇含量達20% (v/v)時，脂雙層疏水及親水頭基區域分子流動性高於在其它乙醇濃度下的分子間流動性。比較V-T與V-α-Tocopherol (VE)奈米聚集體的物理性質結果，可得知PEG側鏈為導致V奈米聚集體膜曲率上升、界面電位上升、膜流動性下降、主相變溫度下降以及穩定天數上升的主要因素。體外滲透結果得知，V滲透量隨T含量增加而下降，可能是PEG側鏈降低V穿透角質層的能力。總累積於皮膚的V含量隨乙醇濃度增加而上升。本研究已經發現最適化的奈米聚集體組成為V/T莫耳比為8/2。

In this study, effects Compound T (T) and ethanol concentration on physical properties of V (V) nanoaggregates were investigated by using transmission electron microscopy (TEM), dynamic light scattering (DLS), fluorescence spectroscopy (FL), and differential scanning calorimetry (DSC). The Franz diffusion cell was used to evaluate in vitro skin permeation ability of V nanoaggregates. Furthermore, the behavior of mixed V/T monolayers at the air/water interface at 25℃ was studied by Langmuir trough technology combined with fluorescence microscopy. Results showed that size and the zeta potential of V nanoaggregates reduced and the morphology of V nanoaggregates changed with increasing amount of T. Addition of T into V nanoaggregates resulted in the occurrence of multiple phase transitions of membrane. When the amount of T increased in V nanoaggregates, temperature of main phase transition (Tm) of V nanoaggregates decreased and fluidity of V membrane increased. Adding small amount of T into V nanoaggregates decreased the molecular mobility in hydrocarbon chain region and interfacial region of membrane at 25℃. As T was incorporated into V monolayer, the mixed monolayer became expended and could be compressed to the high surface pressure. Mixed V/T 8/2 monolyer was more thermodynamically stable than other compositions. When the ethanol concentration increased from 2 to 5% (v/v), the size of V nanoaggregates decreased. The zeta potential was changed from slightly negative into almost neutral value with increasing ethanol concentration (2-20%). When the ethanol concentration increased in V/T nanoaggregates, main phase transition temperature (Tm) of nanoaggregates decreased and fluidity of membrane increased. The molecular mobility increased in hydrocarbon chain and interfacial region of membrane, as the ethanol content reached to 20% in V nanoaggregates. By comparing the results of physical characteristics of mixing V/T with V/α-Tocopherol (VE) nanoaggregates systems, the PEG-chain was the major factor on influencing membrane curvature, zeta potential, main phase transition temperature, membrane mobility, and stable days. From results of in vitro skin permeation study, the accumulstion of V in the skin decreased with increasing the amount of T. This indicated that PEG-chain could be a barrier for skin penetration of drugs. But, the accumulation of V in the skin increased with increasing the ethanol concentration. The optimal formulation, V/T nanoaggregates with the molar ratio of 8/2, was obtained.

摘要 i
Abstract ii
誌謝 iv
目錄 v
表目錄 viii
圖目錄 x
第一章 緒論 1
1-1前言 1
1-2 動機 2
第二章 文獻回顧 3
2-1 V (V) 3
2-2 Compound T (T) 4
2-3乙醇 (EtOH) 5
2-4 單分子層 (Monolayer) 6
第三章 實驗設備與方法 9
3-1 實驗藥品 9
3-2 實驗方法 10
3-2-1 粒徑量測 10
3-2-2 界面電位量測 11
3-2-3 穿透式電子顯微鏡型態觀察 12
3-2-4 螢光偏極化量測 13
3-2-5 微分掃描式熱卡計量測 14
3-2-6 體外皮膚滲透實驗 15
3-2-7 單分子層技術 16
3-2-7-1 Langmuir trough 量測原理 16
3-2-7-2表面壓-分子佔據面積等溫線量測 17
3-2-7-3 混合單分子層過剩面積分析 18
3-2-7-4 混合單分子層過剩自由能分析 19
3-2-7-5 混合單分子層混合自由能分析 19
3-2-7-6 混合單分子層螢光影像觀察 20
第四章 結果與討論 27
4-1 混合V/T奈米聚集體分散液之物理特徵 27
4-1-1型態觀察 27
4-1-2粒徑及界面電位 27
4-1-3相變行為 28
4-1-4螢光偏極化 29
4-2混合V/VE奈米聚集體分散液之物理特徵 30
4-2-1型態觀察 30
4-2-2粒徑及界面電位 30
4-2-3相變行為 30
4-2-4螢光偏極化 31
4-3 PEG側鏈對奈米聚集體特性影響 31
4-4 混合V/T單分子層 33
4-4-1 表面壓-每分子佔據面積等溫線行為 33
4-4-2 熱力學性質分析 34
4-4-2-1 混合V/T單分子層的過剩面積分析 34
4-4-2-2 混合V/T單分子層的過剩自由能與混合自由能分析 34
4-4-2-3 混合V/T單分子層螢光成像 35
4-5固定乙醇含量下經皮吸收分析 37
4-6 不同乙醇含量對混合V/T奈米聚集體分散液之物理特徵影響 38
4-6-1 型態觀察 38
4-6-2粒徑及界面電位 38
4-6-3相變行為 40
4-6-4螢光偏極化 41
4-7固定V/T比例下經皮吸收分析 43
第五章 結論 117
參考文獻 119
附錄一 124

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