界面活性劑與囊胞作用之研究

The Interactions between Surfactants and Vesicles

黃奎鈞(Kuei-Chun Huang)

指導教授 ： 諶玉真

國立臺灣大學/工學院/化學工程學研究所/碩士(2008年)

https://doi.org/10.6342/NTU.2008.00899

摘要

在藥物輸送系統上（Drug Delivery System, DDS），人們希望藥物具有控釋性（controlled release）及標定性（targeting)，也就是人體服用藥物後，能將藥物運達目標部位，再以理想速率釋出有效劑量，並維持我們所期望之有效時間，為了達到目的，藥物載體的選擇很重要。由於囊胞結構之微脂粒有良好的生物可分解性（biodegradable)以及生物相容性（compatible)，因此常被人們當作藥物的載體，其可依目的製備成期望之大小、單多層、及帶電荷量，也可在外層接上不同之官能基，使其可以對特定目標具有標定性，加上其低毒性之優點，故微脂粒為現今之熱門藥物載體。然而人體內有許多界面活性劑可能會破壞囊胞之穩定性，使其達不到預期療效，甚至傷害人體內健康細胞。所以深入地了解界面活性劑與囊胞之間的作用，是藥物輸送系統中，一個十分重要的課題。
在本論文中我們以耗散粒子動力學法模擬界面活性劑對囊胞的影響，在界面活性劑濃度低時，界面活性劑會部分分佈在溶劑中，部份進入囊胞之雙層結構中。而分佈係數為Db / Dw(L+Db)，其中Db為界面活性劑在雙層結構中之濃度，Dw為界面活性劑在溶劑中之濃度，L為脂質濃度。經過我們之計算得知，界面活性劑疏水鏈段之疏水性越強則分佈係數越大；而界面活性劑在親水端的親水性較強時，會較傾向於留在溶劑當中，即分佈係數越小。當界面活性劑濃度增加，達到一臨界值時，囊胞會開始溶解（solubilization），而此時在雙層結構中的界面活性劑濃度及構成囊胞之脂質（lipid）濃度比值Reb值，是一個界面活性劑溶解能力強弱的指標，當界面活性劑疏水鏈段越長，或是斥力參數越大，即疏水性較強時，會得到較大之Reb值，表示當尾巴疏水性強的時候，界面活性劑對囊胞的破壞性比較差。而親水鏈段越長，或是親水頭基斥力參數越小，即親水性較強時，會得較小之Reb值，故我們知道當界面活性劑親水性較高時，只需要較低濃度就能破壞囊胞穩定性。
最後我們將研究不同濃度界面活性劑下，囊胞之型態（morphology）改變，大體來說，在界面活性劑低濃度時囊胞存在無恙，隨著濃度增加囊胞開始產生破洞，而再提高濃度後，構成囊胞之lipid仍大團聚集但已非囊胞型態，過量之界面活性劑濃度便會使得囊胞完全破碎形成混合微胞。

關鍵字

耗散分子動力學 ； 界面活性劑 ； 囊胞 ； 微脂粒 ； 溶解作用

並列摘要

The goal of all sophisticated drug delivery systems (DDS) is to deploy medicines completed to specifically targeted parts of bodies through a medium which can control the administration of the therapy by means of either a chemical or physiological trigger. To achieve the goal, researchers are turning to advances in the world of nanotechnology. During the past decades, lipsomes have been shown to be effective in enhancing drug targeting specificity, improving treatment absorption rates, lowering systemic drug toxicity, and providing protections for pharmaceuticals against biochemical degradation, therefore lipsomes are widely used as drug carriers. Nevertheless, the in vivo stability of liposomes poses limitations on their applications. For example, an enough amount of biosurfactant can solubilize liposomes. Thus, the understanding of the solubilization of liposomes is of great importance.
In this work, the dissipative particle dynamics (DPD) is employed to investigate the interactions between surfactants and vesicles (liposomes). In general, liposome solubilization can be described by the three-stage hypothesis, including vesicular region, vesicle-micelle coexistence, and mixed micellar region. First, we focus on the first stage and study the partition of surfactants between the bilayer phase and the aqueous phase. The partition coefficient K can be related to the surfactant concentration in the bilayer, Db, and that in the solution, Dw, for a given concentration of lipid, L, by Db/Dw(L+Db). A higher value of K indicates that more surfactant molecules are incorporated in the bilayers. As the “hydrophobicity” of surfactants increase, K increases and vice versa. The hydrophobicity of surfactants can be achieved by increasing tail length or the repulsive interaction between tail and water. When the amounts of surfactants reach a critical point, the solubilization begins and the coexistence of vesicles and mixed micelles is found. At this time, the surfactant in lipid phase/lipid molar ratio Re is defined as Reb, which is found to rise as the hydrophobicity of surfactants increases. The results indicate that surfactant with less hydrophobicity has stronger ability to damage the vesicle construction. Further increase of the surfactant concentration results in total collapse of the vesicle. Our simulations clearly observed the process of the liposome solubilization and confirm the validity of the three-stage hypothesis.

並列關鍵字

dissipative particle dynamics ； Surfactant ； Vesicle ； lipsome ； solubilization ； Drug Delivery System

參考文獻

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