- 學位論文
卵磷脂與膽鹽於水溶液中自組裝結構與流變性質研究
Self-assembled Structures and Rheological Properties of Lecithin/Bile Salt Mixtures in Aqueous Solution
摘要
生物界面活性劑在水溶液中的自組裝行為與生理機制有直接相關性，所以一直是很重要的研究議題。最常見的兩種生物界面活性劑是卵磷脂與膽鹽，這兩種介面活性劑都會出現在消化系統當中。卵磷脂與膽鹽由於其多樣的結構以及能夠分別在高極性以及低極性溶劑內自組裝而眾所皆知。在本篇論文內，我們著重於卵磷脂與膽鹽的自組裝結構在水溶液中的形成及其對流變性質的影響。我們發展出兩種控制該混合物於水溶液中自組裝結構及流變性質的方法 （a） 增加電解質濃度 (b) 提高卵磷脂濃度。因為我們的系統是在水溶液內，所以預期這些研究能夠大幅提升於藥物輸送與控制釋放等應用的可能性。 第一部分我們報導一個在水溶液中形成卵磷脂與膽鹽混合物蠕蟲狀微胞的方法，且這些蠕蟲狀微胞具有足夠的長度使溶液黏度提升一千倍。該蟲狀微胞能更進一步的互相糾纏而使溶液具有黏彈性質。在水溶液中，具有較高溶解度的膽鹽能夠與較低溶解度的卵磷脂頭基相互鍵結。在本系統中卵磷脂與膽鹽的莫爾比例對於形成的自組裝形狀及大小扮演關鍵的角色。在一些特定的比例下，卵磷脂與膽鹽於水溶液中的混合物能夠被一些鹽類（如氯化鈉、氯化鈣等）誘導形成長且柔軟的蠕蟲狀微胞。我們使用流變儀、X光與中子散射及冷凍穿透式電子顯微鏡研究流變行為及自組裝結構，並且提出基於有效分子幾何形狀及離子強度誘導形成各種自組裝結構及流變性質的機制。 在第二部分我們討論卵磷脂濃度對其與膽鹽混合物於純水中自組裝結構的影響。我們發現卵磷脂與膽鹽於純水中以低比例混合時能形成一種特殊的水凝膠。此凝膠能形成的最低重量百分濃度為15％。動態流變測試能確認該水溶液的固體性質。我們也使用低溫穿透式電子顯微鏡及小角度X光及中子散射技術去研究自組裝結構，並且由各種證據得知該水凝膠是由澎潤的多層囊泡（脂質體）形成，而非常見的柱狀分子形成的網狀結構。脂質體澎潤現象的機制能被基於卵磷脂層狀結構中穿插膽鹽而形成的表面強排斥力清楚解釋。除了水凝膠之外，還能經由提高混合比例形成一系列的不同流變性質的流體，包括黏彈體、類凝膠及低黏度流體。上述豐富的流變性質溶液是由於不同的卵磷脂與膽鹽混合莫爾比例造成有效分子幾何形狀的改變，進而使層狀結構轉變成柱狀結構最後形成球狀結構。 關鍵字：卵磷脂、膽鹽、自組裝、黏彈體、凝膠
並列摘要
Self-assembly of biological surfactants in water is an important topic for study because of its relevance to physiological processes. Two common types of biosurfactants are lecithin (phosphatidylcholine) and bile salts, which are both present in bile and involved in digestion. Lecithin and bile salts are well known for their diversity of structure and ability to self-assemble in both polar and non-polar solvents. In this thesis, we focus on controlling micellar structures and rheological properties of the mixtures in water. We seek to obtain methods to control self-assembled structure and then to influence rheological properties. Two controlling methods are studied: (a) increasing electrolyte concentration in solution; (b) increasing concentration of lecithin in pure water. While our focus is self-assembly in water, we note that controlling rheological property of aqueous solution can largely enhance possibility for applications such as drug delivery and controlled release. In first part, we report a route for forming lecithin/bile salts wormlike micelles in water that are long enough to enhance the viscosity by more than three orders of magnitude. The wormlike micelles can even entangle into transient network and transform the solutions into viscoelastic fluids. In water, highly soluble bile salt molecules bind the headgroup of lecithin and stabilize the low-water-soluble lecithin. The molar ratio of bile salt to lecithin plays a key role in determining the shape and size of micellar structures. At a specific molar ratio and sufficient ionic strength that is tuned by the addition of electrolytes, such as NaCl and CaCl2, the mixed micelles grow longitudinally into long, flexible chains. We utilize rheology, cryogenic transmission electron microscopy and small-angle neutron and X-ray scattering technologies to study the rheological properties and self-assembly structures, and we propose a mechanism based on the change of molecular geometry caused by the insertion of bile salts and the addition of electrolytes to explain the micellar self-assembly. In the second part, we discuss the effect of lecithin concentration on self-assembly of the mixtures of lecithin/bile salts in water. We reveal an unusual biological hydrogel formed by mixing bile salts and lecithin at low bile salt/lecithin molar ratios in water. The gel can be prepared at a total lipid concentration as low as ~ 15 wt%. The solid-like property of the solutions was confirmed by dynamic rheological measurements. We used cryo-TEM and SAXS/SANS techniques to probe the self-assembled structure and clearly evidence that the gel is made up of jammed swollen multilamellar vesicles (liposomes), instead of typical fibrous networks found in conventional gels. A mechanism based on the strong repulsion between bilayers due to the incorporation of negatively charged bile salts is proposed to explain the swelling of the liposomes. In addition to gel, a series of phases, including viscoelastic, gel-like, and low-viscosity fluids, can be created by increasing the bile salt/lecithin molar ratio. Such a variety of phase behaviors are caused by the transformation of bilayers to cylindrical and spheroidal micelles upon the change of the effective molecular geometry with the bile salt/lecithin molar ratio.