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標題: | Pluronics之界面性質及其與膽固醇/DPPC混合膜
之相互作用 Interfacial Properties of Pluronics and Interactions between Pluronics and Cholesterol/DPPC Mixed Monolayers |
作者: | Yao-Yu Chang 張耀宇 |
指導教授: | 高純琇 |
關鍵字: | 膽固醇,界面,單層膜,等溫曲線,界面活性劑,細胞膜, cholesterol,pluronic,DPPC,surfactant,membrane,monolayer,isotherm, |
出版年 : | 2007 |
學位: | 碩士 |
摘要: | 中文摘要
Pluronic為三嵌段聚合物,由聚環氧乙烷(PEO)以及聚環氧丙烷(PPO)所組合而成,其為非離子界面活性劑且有廣泛的hydrophilic-lipophilic balance (HLB),所以在藥劑學上已被廣泛的應用與研究。近來研究發現,Pluronic可以填補至受損的細胞膜上,當細胞修補好時又會自動地離開,藉由Pluronic和細胞膜的各種交互作用機制,也有可能可以成為藥物治療的方法之一。所以本論文欲運用界面的技術,探討Pluronic於空氣/水界面的性質與其化學結構之關係,再利用穿透動力學實驗來研究Pluronic與膜脂質所形成單分子層之間的交互作用。 觀察Pluronics於25 oC的Π-A等溫曲線且綜合表面彈性的變化,可知大部分的Pluronics會出現兩個相轉換,根據相轉換時平均分子所佔面積的分析,發現相轉換I主要與Pluronic的PEO長鏈之EO單體數有關,而相轉換II主要是受PPO長鏈之PO單體數影響。 在Pluronic與DPPC單分子層之相互作用實驗中,在Pluronic於下層液之濃度為2 x 10-4 mg/mL的條件下,Pluronic穿透至DPPC的能力與其PEO、PPO長鏈長短以及分子量有關,而平衡時的膜壓改變量對初始膜壓作圖呈線性關係,且高於理論曲線,而且當初使膜壓越高時,平衡膜壓改變量較理論曲線更高,代表下層液的Pluronic與分散於空氣/水界面的DPPC可能有吸引力的存在。在膽固醇/DPPC 20/80及40/60 mol%混合單層膜之實驗結果,則顯示膽固醇會使混合膜穩定,且在高的表面壓力下會更穩定。在Pluronics與膽固醇/DPPC 40/60 mol%混合膜的交互作用實驗中,因膽固醇上的3β-hydroxyl官能基會與PEO長鏈上的ether oxygen有較明顯的氫鍵吸引力,而有F68與混合膜間有較顯著且高於其與DPPC之交互作用結果;而對同PEO數不同PPO數之Pluronic而言,因膽固醇上的3β-hydroxyl與PPO長鏈上的ether oxygen的氫鍵吸引力較弱,而呈現其與DPPC或混合膜具相同吸引力的結果;Pluronic L35則因其在單位重量有較多之尾端的OH基,而與混合膜有較顯著且高於其與DPPC之交互作用。 本研究所得之關於Pluronic結構對其與膜脂質如DPPC、膽固醇之交互作用關係的影響,將有助於了解Pluronic在藥劑上作為藥物載體之各種研究結果。 英文摘要 Triblock copolymers of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) are nonionic surfactant with wide range of hydrophilic-lipophilic balance (HLB). They have been used and investigated extensively in pharmaceutical researches. Recently, pluronics were found to be able to seal broken cell membranes and then leave as the cell membranes restored. This special function of Pluronics might provide a new therapeutic route. The aim of the present study is to investigate the relationship between Pluronics, chemical structures and their interfacial properties at the air/water interface by surface techniques, and the interactions between pluronics and membrane lipid monolayers by penetration experiments. Combining the results of Π-A isotherms and surface elasticity of Pluronics monolayers at 25 oC, most Pluronics appeared two phase transitions. According to the analysis, it was found that the phase transition I was mainly affected by the number of EO monomers of the Pluronics, and the phase transition II was mainly affected by the number of PO monomers. In the study of interactions between Pluronics and DPPC monolayers, under condition of Pluronics 2 x 10-4 mg/mL in subphase, the penetration ability of Pluronics to DPPC monolayers was determined by PEO、PPO chains length and molecule weight of the Pluronics,. It was found that more Pluronics molecules may penetrate into DPPC interface than expectedwhen compared the penetration results with a theoretical line of no interaction. It suggested that some kinds of attractive interactions may exist between Pluronics and DPPC monolayers. The Π-A isotherms of cholesterol/DPPC 20/80 and 40/60 mol% mixed monolayers indicated that the cholesterol would stabilize the mixed monolayers especially at higher surface pressures. In the study of interactions between Pluronics and Chol/DPPC 40/60 mol% mixed monolayers, it is most likely that hydrogen bond attractions may exist between the 3β-hydroxyl of the cholesterol and ether oxygen of PEO chains. Such interactions may lead Pluronic F68, a Pluronic with the longest PEO chain in this study, to exhibit obviously higher penetration ability than the others. As for Pluronics with the same EO number but different PO numbers, they exhibited almost equal attractive interaction with DPPC monolayers and Chol/DPPC mixed monolayers due to a weaker hydrogen bond attractions between the 3β-hydroxyl of cholesterol and ether oxygen of PPO chains. In the series of Pluronic L35、P65 and P105, L35 has more hydroxyl end groups per unit weight than the others, the attractions between L35 and mixed monolayers were higher than L35 and DPPC monolayers. The results of this study provide us information to know how the structure of Pluronics affected the interactions between Puronics and membrane lipids such as the DPPC and the cholesterol. It would help us to understand the behavior of Pluronics observed in other studies such as the research of drug delivery systems. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/28043 |
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