Allen T M, Hansen C, Martin F, Redemann C, Yau-Young A
Department of Pharmacology, University of Alberta, Edmonton, Canada.
Biochim Biophys Acta. 1991 Jul 1;1066(1):29-36. doi: 10.1016/0005-2736(91)90246-5.
Novel synthetic lipid derivatives of poly(ethylene glycol) (PEG) have been synthesized and tested for their ability to decrease uptake of liposomes into the mononuclear phagocyte system (MPS, reticuloendothelial system) in mice and to prolong circulation half-lives of liposomes. A carbamate derivative of PEG-1900 with distearoylphosphatidylethanolamine (PEG-DSPE) had the greatest ability to decrease MPS uptake of liposomes, at optimum concentrations of 5-7 mol% in liposomes composed of sphingomyelin/egg phosphatidylcholine/cholesterol (SM/PC/Chol, 1:1:1, molar ratio). Results obtained with this compound were equivalent to results previously obtained with 10 mol% monosialoganglioside GM1 in liposomes of similar compositions (Allen, T.M. and Chonn, A. (1987) FEBS Lett. 223, 42-46). Non-derivatized methyl PEG or PEG-stearic acid (PEG-SA) were incapable of decreasing MPS uptake of liposomes. PEG-Chol and PEG-dipalmitoylglycerol (PEG-DPG) were intermediate in their effects on MPS uptake. Altering liposome size for liposomes containing PEG-DSPE resulted in only minor changes in blood levels of liposomes. Half-lives of 0.1 microns liposomes of SM/PC/Chol/PEG-DSPE (1:1:1:0.2, molar ratio) in circulation was in excess of 20 h following either i.v. or i.p. injection. Liver plus spleen liposome levels for these liposomes was below 15% of injected label at 48 h following i.v. liposome injection and below 10% following i.p. injection. The major site of liposome uptake was in carcass tissues, with over 50% of label remaining in vivo at 48 h post-injections, either i.v. or i.p., in the carcass.
已合成聚乙二醇（PEG）的新型合成脂质衍生物，并测试了它们降低小鼠单核吞噬细胞系统（MPS，网状内皮系统）对脂质体摄取以及延长脂质体循环半衰期的能力。在由鞘磷脂/卵磷脂/胆固醇（SM/PC/Chol，摩尔比1:1:1）组成的脂质体中，PEG - 1900与二硬脂酰磷脂酰乙醇胺的氨基甲酸酯衍生物（PEG - DSPE）在5 - 7 mol%的最佳浓度下具有最大的降低脂质体MPS摄取的能力。用该化合物获得的结果与先前在类似组成的脂质体中使用10 mol%单唾液酸神经节苷脂GM1获得的结果相当（Allen, T.M.和Chonn, A.（1987年）《欧洲生物化学学会联合会快报》223, 42 - 46）。未衍生化的甲基PEG或PEG - 硬脂酸（PEG - SA）无法降低脂质体的MPS摄取。PEG - Chol和PEG - 二棕榈酰甘油（PEG - DPG）对MPS摄取的影响处于中等水平。改变含有PEG - DSPE的脂质体大小只会导致脂质体血液水平的微小变化。SM/PC/Chol/PEG - DSPE（摩尔比1:1:1:0.2）的0.1微米脂质体在静脉内或腹腔内注射后，循环半衰期超过20小时。在静脉内注射脂质体后48小时，这些脂质体在肝脏加脾脏中的水平低于注射标记物的15%，腹腔内注射后低于10%。脂质体摄取的主要部位是胴体组织，静脉内或腹腔内注射后48小时，超过50%的标记物留在胴体中的体内。
