Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/3837
標題: 含脂質高分子液胞通道酸鹼應答性探討
pH-Induced Regulation of Transmembrane Channels of Lipid-Containing Copolymer Vesicles
作者: 林素貞
Lin, Su-Chen
關鍵字: Ca2+
螯合
screening
chelating
凝降作用
出版社: 化學工程學系所
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摘要: 本研究中採用的脂質共聚合高分子poly(acrylic acid-co-distearin acrylate)是以聚丙烯酸poly(acrylic acid , AAc)為主鏈,側鏈上修飾不同比例的二硬脂酸甘油脂(distearin),利用二次乳化法(double emulsion)製備出具有酸鹼應答性的微米級高分子液胞(pH-responsive vesicles),並探討四種不同DSA組成比的高分子液胞(分別為10mol%、13 mol%、15 mol%、18 mol%),首先由光學顯微鏡(OM) 觀察液胞形態,接著利用掃描式電子顯微鏡(SEM)和雷射掃描式共軛焦顯微鏡(LSCM)證實為高分子液胞結構,並於液胞溶液中加入水溶性螢光物質(如:calcein及不同分子量的FITC-dextran),由LSCM觀察酸鹼應答穿膜通道的應答情形。發現通道開啟的pH隨DSA含量增加而上升,且液胞穩定性亦隨之上升。有趣的是,若於不同pH添加鈣離子(5×10-3M)與解離之AAc單元因靜電交互作用力產生螯合(chelation),不僅能有效提高液胞的穩定性,亦能使高分子液胞膜層對穿膜的水溶性分子具有大小的選擇性(size selection)。另外,鈣離子的加入也會造成高分子液胞的穿膜通道應答pH降低,使酸鹼應答穿膜通道於較低pH開啟,其主因推測為隨著鈣離子與AAc單元螯合,而產生類似交聯的情形使液胞膜層發生凝降作用(screening effect),使原本因解離而伸展之polyAAc鏈段因交聯而凝降進而產生縫隙,降低液胞膜層因高分子鏈纏繞的立體障礙,使親水分子可通過液胞膜層。經由上述的發現,高分子液胞於不同的pH環境下,對穿膜的水溶性分子大小具選擇性。此一結果展現出此高分子液胞於藥物控制釋放的應用上,具很高的潛力。
In this study, polymer vesicles attained from self-assembly of copolymers comprising monomeric units of acrylic acid (AAc) and distearin acrylate (DSA) in microsized scale are imparted pH-responsive transmembrane channels permeable to hydrophilic cargoes. The vesicle assemblies were prepared using double emulsion technique in a water-in-oil-in-water manner and examined mainly by laser scanning confocal microscopy (LSCM). The critical pH value that induces the channels' open and closure depends mainly on the DSA contents of copolymers and, once being open, the channel size can be further enlarged with increasing the external pH. On the other hand, the channel size reduces with increasing the DSA content of the copolymer employed for the vesicle assembly, owing to the increases in both the packing density and area of the lipid bilayer islets within the vesicle walls. While the vesicle assemblies become gradually unstable and transformed into micelle structure upon the pH-induced channels' open, the vesicle structure can be effectively stabilized by addition of Ca2+ ions in the aqueous vesicle suspensions as primarily a result of the cross-linking effects from the chelating action of Ca2+ ions with ionized AAc residues. Concomitantly, the screening from Ca2+ ions with ionized AAc residues facilitates the channels' open by showing a significant reduction in the critical pH. The vesicles capable of undergoing pH/Ca2+-induced morphological regulation in transmembrane channel size in terms of their permeability to hydrophilic cargoes of varying sizes thus show great potential in drug delivery applications by providing facile control of (polar) drug encapsulation and release.
URI: http://hdl.handle.net/11455/3837
其他識別: U0005-2206201016510200
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-2206201016510200
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