【作者】 乔华； 李波； 卞伟；

【Author】 Hua Qiao;Bo Li;Wei Bian;School of Basic Medical Sciences, Shanxi Medical University;

【机构】 山西医科大学基础医学院；

【摘要】 脂质体作为药物载体在医药领域中得到了广泛的应用。为了提高脂质体的携载能力,常在其组成体系中加入阳离子表面活性剂,然而一些常用阳离子表面活性剂会影响血液中及细胞膜表面蛋白的构象使其丧失生理功能,限制了脂质体的应用范围。为此,本工作考察了类脂质阳离子表面活性剂双十二烷基二甲基溴化铵(DDAB)、非离子表面活性剂吐温80(Tween 80)及二者1︰1复配体系对血清蛋白的影响。首先以牛血清白蛋白为模型蛋白,采用多光谱联用技术考察了DDAB、Tween 80及DDAB–Tween 80(1︰1复配体系)对其构象的影响;在此基础上,采用相同的方法考察了DDAB、Tween 80及DDAB–Tween 80对人血液中五种常见主要蛋白——人血清白蛋白、载脂蛋白A1、转铁蛋白、纤维原蛋白及免疫球蛋白G的影响,并在人血清中进行了验证。结果表明,DDAB–Tween 80对各种蛋白的影响都明显低于DDAB和Tween80,这一结果为阳离子–非离子复配体系组成脂质体降低毒副作用、提高药效提供了一定理论依据。更多还原

【Abstract】 Liposomes are a common delivery vehicle for drugs, but some common surfactants used as liposome components may cause denaturation and malfunction of serum proteins. Here, we examined the effects of didodecyldimethylammonium bromide(DDAB), polyoxyethylene sorbitan monooleate 80(Tween 80), and the equimolar mixture on the properties of serum proteins. Bovine serum albumin was selected as the model protein,and the effects of the DDAB, Tween 80, and a 1:1 mixture on its spectroscopic behavior were investigated. The effects of surfactants on the five major serum proteins: human serum albumin, apolipoprotein A1, transferrin,fibrinogen and immunoglobulin G were also examined. Finally, the results were verified on human serum. The results indicated that weak interactions exist between human serum proteins and the DDAB–Tween 80,significantly different from the strong interactions of DDAB and Tween 80 with proteins. The salient features of cationic–nonionic surfactants enable their use in liposome composition.更多还原