LIPOSOMES CONTAINING SYNTHETIC LIPID DERIVATIVES OF POLY(ETHYLENE GLYCOL) SHOW PROLONGED CIRCULATION HALF-LIVES INVIVO
LIPOSOMES CONTAINING SYNTHETIC LIPID DERIVATIVES OF POLY(ETHYLENE GLYCOL) SHOW PROLONGED CIRCULATION HALF-LIVES INVIVO
复制标题
DOI：
10.1016/0005-2736(91)90246-5
复制
发表时间：
1991-07-01
期刊：
影响因子：
--
通讯作者：
YAUYOUNG, A
中科院分区：
文献类型：
--
作者：
ALLEN, TM;HANSEN, C;YAUYOUNG, A
合成了聚乙二醇（PEG）的新型合成脂质衍生物，并测试了其降低小鼠单核吞噬细胞系统（MPS，网状内皮系统）对脂质体的摄取和延长脂质体循环半衰期的能力。PEG-1900与二硬脂酰磷脂酰乙醇胺（PEG-DSPE）的氨基甲酸酯衍生物在由鞘磷脂/卵磷脂/胆固醇（SM/PC/Chol，1：1：1，摩尔比）组成的脂质体中的最佳浓度为5- 7mol%时具有最大的降低脂质体的MPS摄取的能力。用该化合物获得的结果与先前用类似组成的脂质体中的10摩尔%单唾液酸神经节苷脂G（M1）获得的结果相当（艾伦，T.M.和Chonn，A. 04 The Dog（1987）223，42-46）。非衍生化的甲基PEG或PEG-硬脂酸（PEG-SA）不能降低脂质体的MPS摄取。PEG-Chol和PEG-二棕榈酰甘油（PEG-DPG）对MPS摄取的影响居中。改变含有PEG-DSPE的脂质体的脂质体尺寸仅导致脂质体血液水平的微小变化。静脉注射或腹腔注射后，SM/PC/Chol/PEG-DSPE（1：1：1：0.2，摩尔比）的0.1 μ m脂质体在循环中的半衰期超过20小时。静脉注射脂质体后48小时，这些脂质体的肝脏和脾脏脂质体水平低于注射标签的15%，腹膜内注射后低于10%。脂质体摄取的主要部位是在尸体组织中，在静脉内或腹膜内注射后48小时，超过50%的标记物留在体内，在尸体上。
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 G(M1) 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-mu-m 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.