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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/24838


    標題: 雙長碳鏈陽離子型界劑與雙十六碳醇磷酸酯組成之奈米液胞應用於包覆藥物及經皮吸收的研究
    Applications of Nano Vesicles Composed of Dialkyldimethylammoniumbromide and Dihexadecyl Phosphate on Drug Encapsulation and Transdermal Absorption
    作者: 周宗翰
    貢獻者: 化妝品應用與管理系
    關鍵字: 液胞
    單分子層
    物化特徵
    細胞測試
    經皮藥物傳遞
    Vesicles
    Monolayers
    Physicochemical characteristics
    Cell tests
    Transdermal drug delivery
    日期: 2010
    上傳時間: 2011-12-22 09:46:43 (UTC+8)
    摘要: 過去數十年來,開發新技術增加藥物穿皮吸收效果方面的研究已經引起廣大的興趣。其中,又以液胞(vesicles)作為輸送藥物的技術特別受到重視。液胞主要是由雙極性分子(amphiphiles)在水溶液中自行聚集而形成雙層結構的載體。本計畫的目的是使用低成本的材料開發一新的包覆5-FU 及蘆薈大黃素(aloe emodin, AE) 載體。藉由三種不同製程,使用具有不同長度側鏈及不同電性極性頭基之雙碳鏈陽離子型界面活性劑 (dialkyldimethylammonium bromides, DXDAB)與雙十六碳醇磷酸酯(dihexadecyl phosphate, DHP)來製備液胞。在此三年計劃中,將深入研究由雙碳鏈陽離子型界面活性劑與雙十六碳醇磷酸酯所組成之單分子層(monolayer)行為與液胞的物化特徵,以及液胞與細胞交互作用的影響。待製備液胞的製程條件確立後,利用此奈米液胞包覆5-FU 及AE。並將藉由藥物包覆效率、藥物釋放速率、儲藏穩定性、體外細胞測試,及藥物穿皮及停留在皮膚的含量等試驗進一步評估這一系列液胞做為經皮吸收藥物載體的能力與可行性。第一年藉由單分子層的技術與界面熱力學的分析深入探討混合DXDAB/DHP 系統與加入添加劑及藥物於混合系統中的薄膜性質以作為液胞製備時所需之資訊。以薄膜水合-超音波震盪法、冷凍-解凍法及開發改良式酒精注射法三種方式製備不同電性與高品質之液胞。並且透過有系統的實驗設計,找出此三種製程的最適化操作參數。 最後,探討單分子層與雙層結構液胞行為的異同之處。第二年利用雷射粒徑暨界面電位分布分析儀、穿透式電子顯微鏡及螢光光譜儀探討液胞組成對其物化性質、薄膜結構、薄膜流動性及儲存穩定性的效應。並研究添加劑對液胞行為的影響。此外,將藉由細胞存活度測試、細胞型態觀察及流式細胞儀分析等細胞測試方法探討不同組成液胞對 A431 與Hs68 兩細胞的影響,並了解液胞的物化特徵對細胞行為的影響。第三年應用此新穎之奈米液胞包覆5FU(親水性藥物)、AE(疏水性藥物)及同時包覆5-FU 與 AE。藉由高效能液相層析儀結合螢光與紫外光偵測器定量5-FU 及蘆薈大黃素(aloe emodin, AE)濃度以分析液胞的包覆藥物效率。並研究在不同溫度及添加劑對包覆藥物液胞的物化特徵、儲存穩定性及藥物釋放行為的影響。 最後,利用體外細胞測試、Franz 擴散槽進行體外動物實驗及動力學模式分析評估這些液胞在經皮吸收的效能及可行性。
    During the past decades there has been wide interest in exploring new techniques to increase drug absorption through skin. Topical delivery of drugs by vesicles has evoked a considerable interest. Vesicles are formed by the self-assembly of amphiphiles in the aqueous media providing bilayer structures. The project purpose is to develop a novel vehicle for trandsermal drug delivery of 5-FU and aloe emodin (AE) by using low cost materials. Dialkyldimethylammonium bromides (DXDAB) and dihexadecyl phosphate (DHP) that have the different lengths of side double-chains and different charges of polar head groups are used to prepare vesicles with three different manufacturing processes. In this three-year project, characteristics of monolayers and vesicles composed of DXDAB and DHP, and vesicle cytotoxicity will be deeply studied first. After the preparation process of vesicles establish, this nano vesicles are utilized to encapsulate 5-FU and AE. The feasibility and ability of these vesicles being used as transdermal drug delivery carriers will be evaluated by encapsulation efficiency, release rate, storage stability, in vitro cell tests, and skin permeation and deposition tests of drug. The First Year The membrane properties of mixed DXDAB/DHP systems with additives will be deeply studied by a Langmuir monolayer technique and the interfacial thermodynamic analysis to obtain the useful information for future manufacture of vesicles. The thin film hydration-sonocation, a free-and thaw with sonication and a modified ethanol injection processes will be developed to prepare vesicles with specific charge characteristic and good quality. Optimum operating parameters for three methods will be found by means of the systematic experiment design. The Second Year The composition effect of vesicles on physicochemical characteristics, membrane structure, and storage stability will be investigated by using a particle-size and zeta potential analyzer, a transmission electronic microscope, and a fluorescent polarization spectrometer. In addition, effects of additives on the vesicles behavior will be studied and interaction of vesicles with A431 and Hs68 cells will be investigated by means of cell viability, cell morphology, and flow cytometry analysis. The Third Year The novel vesicles are applied to encapsulate a hydrophilic drug, 5FU, a lipophilic drug, AE, and simultaneously 5-FU and AE. The encapsulation efficiency of vesicles for carrying drugs will be analyzed respectively by high performance liquid chromatography with fluorescence and UV detectors. The physicochemical properties, storage stability and releasing behavior of vesicles containing drugs and additives will be studied at different temperatures. Finally, the feasibility and ability of vesicles on transdermal adsorption will be evaluated by in vitro cell tests, Franz diffusion cells and the dynamic model analysis.
    關聯: 計畫編號:NSC99-2221-E041-020
    計畫年度:99;起迄日期:2010-08-01~2011-07-31
    核定金額:842,000元
    Appears in Collections:[化妝品應用與管理系(所)] 國科會計畫

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