In vivo applications of PEG liposomes: unexpected observations.
In vivo applications of PEG liposomes: unexpected observations.
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PEG 脂质体的体内应用：意想不到的观察结果。
DOI：
10.1615/critrevtherdrugcarriersyst.v18.i6.40
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发表时间：
2001
影响因子：
2.7
通讯作者：
G. Storm
中科院分区：
文献类型：
--
作者：
P. Laverman;O. Boerman;Oyen WJG;Corstens FHM;G. Storm
最近在患者中使用PEG脂质体的研究一致表明，脂质体可诱导副作用（潮红、胸闷）。此外，PEG脂质体的血液清除率显示出剂量依赖性：在低于1 μ mol/kg的脂质剂量下，PEG脂质体不显示长循环特性，而是相对快速地从血流中清除。另一个值得注意的观察结果是重复注射PEG脂质体导致显著的药代动力学变化：第二剂放射性标记的PEG脂质体的循环半衰期在第一次注射后5天至4周内显著降低。在这三种意想不到的现象中，补体系统的蛋白质似乎起着关键作用。因此，必须考虑PEG脂质体不是体内惰性载药载体。无论药物含量如何，仅通过使用脂质体颗粒即可诱导产生药理学效应。
Recent studies with PEG liposomes in patients have consistently shown that liposomes can induce side effects (flushing, tightness of the chest). Furthermore, the blood clearance of PEG liposomes was shown to be dose-dependent: at lipid doses lower than 1 micromol/kg, PEG liposomes do not show the long-circulation property but instead are cleared relatively rapidly from the bloodstream. Another remarkable observation was that repeated injections of PEG liposomes led to significant pharmacokinetic changes: the circulatory half-life of a second dose of radiolabeled PEG liposomes dramatically decreased when given from 5 days to up to 4 weeks after a first injection. In these three unexpected phenomena, proteins of the complement system seem to play a key role. Therefore, one has to consider that PEG liposomes are not inert drug-carrying vehicles in vivo. Pharmacological effects can occur, induced solely by using liposomal particles irrespective of the drug content.