溫度和PEG-脂質對磷脂醯膽鹼與離子型界面活性劑間作用的影響之研究; The Interactions between Phosphatidylcholine Vesicles and Ionic Surfactants : Temperature and PEG-Lipid

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Title:	溫度和PEG-脂質對磷脂醯膽鹼與離子型界面活性劑間作用的影響之研究;The Interactions between Phosphatidylcholine Vesicles and Ionic Surfactants : Temperature and PEG-Lipid
Authors:	朱世琪;Shih-Chi Chu
Contributors:	化學工程與材料工程研究所
Keywords:	微脂粒;離子型界面活性劑;溫度;PEG-脂質;電導度;ionic surfactants;liposome;PEG-lipd;Conductivity;temperature
Date:	2002-06-05
Issue Date:	2009-09-21 12:20:17 (UTC+8)
Publisher:	國立中央大學圖書館
Abstract:	溫度和PEG-脂質對磷脂醯膽鹼與離子型界面活性劑間作用的影響之研究學生：朱世琪指導教授：曹恒光國立中央大學化學工程與材料工程研究所中文摘要由於微脂粒的特殊結構和性質，所以常被應用於當作控制釋放的載體，然而在體內會受到生物型的界劑影響，導致溶解現象發生。一般而言，界劑溶解微脂粒溶解過程可區分成微泡區、共存區、及混合微胞區。本論文將探討微泡區中，脂質和水相環境的界劑分佈平衡常數K。本研究以擠壓法(extrusion)製備實驗所需要的微脂粒且皆不含有鹽類與緩衝溶液，並透過電導度量測來探討離子型界劑對微脂粒的溶解作用。所使用的六種界劑包含不同的疏水基鏈長 (C10-C16)及陰陽二種離子性頭基，並在三種溫度及添加PEG-脂質的條件下進行實驗。基於界劑溶解微脂粒的機制，界劑會嵌入脂雙層的行為，如同電荷會束縛於其中，因此界劑溶液含有微脂粒會造成電導度的下降，所以我們藉由電導的變化可決定界劑的K及Reb。所得到熱力學參數皆都能符合熱力學限制(J. Chem. Phys. 2001, 115, 8125)。實驗結果發現K值會隨著溫度升高而下降，其標準化學勢(chemical potential)差異的級數為kT，並且隨著疏水基鏈長的增加而上升，這結果表示每一個在水相的界劑分子其平均作用能大於在脂質相的。改變溫度會使得界劑嵌入脂雙層勝於形成微胞，因此其溶解的能力會隨著K值上升而下降。對於特別的極性頭基，其分佈常數隨著鏈長增加而增加。根據實驗結果發現，符合熱力學的預期，界劑的每一個烷基內能級數為kT。由於立體障礙力使得包含PEG –lipid的微脂粒其物理穩定性增加，從生物穩定性來看添加PEG –lipid的微脂粒減少了被嗜菌細胞吞噬的機會。在我們的研究系統中若添加1 ％的PEG（2000）–lipid，則其粒徑比無添加PEG—lipid的微脂粒較小。此外，熱力學參數K和Reb皆上升。實驗結果顯示添加PEG-lipid可降低界劑在脂質相的平均自由能，導致得到較大的平衡常數，且提升微脂粒抵抗界劑溶解的能力。因此我們認為添加PEG-lipid可提供另一個穩定的機制。 The Interactions between Phosphatidylcholine Vesicles and Ionic Surfactants: Effects of Temperature and PEG-Lipid Student: Shis-Chi Chu Advisor: Heng-Kwong Tsao Department of Chemical and Materials Engineering National Central University ABSTRACT Liposomes are widely used as drug carriers due to their special structure and properties. Nevertheless, the in vivo stability of liposomes poses limitations on their applications. For example, an enough amount of biosurfactant can solubilize liposomes. In general, liposome solubilization can be described by the three-stage hypothesis, including vesicular regime, vesicle-micelle coexistence, and mixed micellar regime. In this thesis, we focus on the first stage and study the partition of ionic surfactant between the bilayer phase and the aqueous phase. Phosphatidylcholine vesicles are prepared by the extrusion method without addition of buffer and salt. The bilyer/aqueous phase partition coefficient K and the surfactant/lipid molar ratio Re of of six ionic surfactants are then determined by conductivity measurements, which are based on the fact the vesicle acts as a trap of charge carriers. The main purpose of the thesis is to investigate the effects of temperature and PEG-lipid on the partition coefficient. The experimental data can be well represented by the simple thermodynamic model and the thermodynamic parameters satisfy the thermodynamic consistency. The partition coefficient is found to decline with increasing temperature. This consequence indicates that the mean interaction energy per surfactant molecule in the aqueous phase mw0 is greater than that in the bilayer mb0. The difference of the mean interaction energy is O(kT) and rises as the chain length is increased. Because the change in temperature influences the surfactant incorporation into the bilayer more than the formation of micelles, the solubilizing ability Reb also decreases in accord with the partition coefficient. For a specified hydrophilic head, we observe that the partition coefficient grows with the alkyl chain length. According to our experimental results, the increment of the mean interaction energy per alkyl group is O(kT), which agrees with the thermodynamic prediction. It is known that the physical stability of a liposome containing a few PEG-lipid is enhanced due to the steric repulsion. Biologically, a stealth liposome is also obtained because PEG-lipid provides the opportunity of escaping from macrophage uptake. In this study, a liposome containing 1% PEG (2000)-lipid is prepared. In comparison with liposomes without PEG-lipid, the mean radius of such liposomes is smaller. In addition, the thermodynamic parameters K and Reb are increased. This result indicates that PEG-lipid lowers the mean interaction energy in the bilayer phase and therefore leads to a higher partition coefficient. However, the ability of resisting surfactant solubilization is also enhanced. Therefore, we conclude that addition of PEG-lipid provides another stability mechanism.
Appears in Collections:	[National Central University Department of Chemical & Materials Engineering] Electronic Thesis & Dissertation

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