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用于生物应用的聚合物稳定的聚乙二醇接枝脂质体与物理吸附的羧甲基壳聚糖及羧甲基/乙二醇壳聚糖脂质体的比较

Comparison of polymerically stabilized PEG-grafted liposomes and physically adsorbed carboxymethylchitin and carboxymethyl/glycolchitin liposomes for biological applications.

作者信息

Mobed M, Chang T M

机构信息

Artificial Cells and Organs Research Centre, McGill University, Faculty of Medicine, Montreal, Canada.

出版信息

Biomaterials. 1998 Jul;19(13):1167-77. doi: 10.1016/s0142-9612(98)00004-0.

Abstract

The stabilities of two types of polymerically stabilized liposomes consisting of PEG-grafted (DSPC:CHOL:DSPE-PEG1900, 5:4:1) and physically adsorbed carboxymethylchitin (CMC) and carboxymethyl/glycolchitin (CO) are compared. The polyelectrolyte is adsorbed on positive (DSPC:CHOL:DMTAP, 5:4:1) and neutral (DSPC:CHOL, 1:1) liposomes at different molecular weights (Mw). In PBS buffer (c(s) = 154 mM, pH = 7.4) the theoretical stability ratios (W) calculated using the classical DLVO Theory, indicate that the CMC-coated vesicles and the negative liposomes (DSPC:CHOL:DMPG, 5:4:1) are highly stable (W >> 1) compared to the PEG-grafted (W = 0.9511) and CO-coated (W = 0.9550) liposomes. Meanwhile, experimentally determined values of W, prove that the PEG-grafted is the most stable suspension (W = 5.5). Computation of the theoretical values of W for liposome-red blood cell and liposome-macrophage indicates that the electrosterically stabilized suspensions and the negative liposomes are stable. Light scattering results show that the flocculation of liposomes in blood and plasma depends on polymer molecular weight, type of polyelectrolyte and surface charge of the uncoated liposome. Neutral liposomes coated with CMC of Mw = 1.01 x 10(5) and negative liposomes provide a more effective barrier to plasma macromolecular protein adsorption than the grafted PEG groups and are easy to resuspend in blood.

摘要

比较了两种类型的聚合物稳定脂质体的稳定性,一种是由聚乙二醇接枝的(二硬脂酰磷脂酰胆碱:胆固醇:二硬脂酰磷脂酰乙醇胺 - 聚乙二醇1900,5:4:1),另一种是物理吸附的羧甲基壳聚糖(CMC)和羧甲基/糖基壳聚糖(CO)。聚电解质以不同分子量(Mw)吸附在阳性(二硬脂酰磷脂酰胆碱:胆固醇:二肉豆蔻酰基 - N,N - 二甲基叔胺丙烷,5:4:1)和中性(二硬脂酰磷脂酰胆碱:胆固醇,1:1)脂质体上。在磷酸盐缓冲盐水(c(s)=154 mM,pH = 7.4)中,使用经典的DLVO理论计算的理论稳定性比(W)表明,与聚乙二醇接枝的(W = 0.9511)和CO包被的(W = 0.9550)脂质体相比,CMC包被的囊泡和阴性脂质体(二硬脂酰磷脂酰胆碱:胆固醇:二肉豆蔻酰磷脂酰甘油,5:4:1)具有高度稳定性(W >> 1)。同时,实验测定的W值证明聚乙二醇接枝的是最稳定的悬浮液(W = 5.5)。脂质体 - 红细胞和脂质体 - 巨噬细胞的W理论值计算表明,电空间稳定的悬浮液和阴性脂质体是稳定的。光散射结果表明,脂质体在血液和血浆中的絮凝取决于聚合物分子量、聚电解质类型和未包被脂质体的表面电荷。Mw = 1.01 x 10(5)的CMC包被的中性脂质体和阴性脂质体比接枝的聚乙二醇基团对血浆大分子蛋白质吸附提供了更有效的屏障,并且易于在血液中重新悬浮。

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