Zeisig R, Eue I, Kosch M, Fichtner I, Arndt D
AG Phospholipids, Max-Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.
Biochim Biophys Acta. 1996 Sep 4;1283(2):177-84. doi: 10.1016/0005-2736(96)00090-9.
The aim of the study was to investigate for the first time the preparation, physical properties and macrophage activating effect of sterically stabilized liposomes made from hexadecylphosphocholine (HPC, Miltefosine) using different poly(ethylene glycol) lipids for coating. We could demonstrate that it is possible to prepare different liposomal vesicle types (MLV, SUV and LUVET) without any problem and with a high stability in buffer (release of hydrophilic marker was < 5% after half a year) and in plasma (t1/2 up to several days). The preparation method, including size of polycarbon membrane filter used for the preparation of LUVETs had the main influence on vesicle size and size distribution. The addition of a charged lipid like DCP and different amounts of PEG-lipid up to 10% had no effect on size and stability of PEG-LUVETs. A comparison of activating potency of PEG-HPC-vesicles with commonly used HPC-liposomes was performed with mouse peritoneal macrophages. HPC-liposomes induced a clear release of NO and TNF from mouse peritoneal macrophages especially in a synergistical action with LPS. On the contrary the effect of PEG-liposomes was similar to control cells after a combined activation in vivo/in vitro. The reduced interaction of these liposomes with the MPS was also demonstrated by an unchanged carbon ink uptake after treatment of mice (i.p.) with liposomes prepared with and without PEG-lipid. PEG-HPC-liposomes combine the advantages of HPC, liposomes and PEG-coating, resulting in a promising preparation for treatment of mammary cancers.
本研究的目的是首次研究用不同聚乙二醇脂质包被的十六烷基磷酰胆碱（HPC，米托蒽醌）制备的空间稳定脂质体的制备、物理性质和巨噬细胞激活作用。我们能够证明，制备不同类型的脂质体囊泡（多层脂质体、小单层脂质体和大单层脂质体）没有任何问题，并且在缓冲液中（半年后亲水性标记物的释放<5%）和血浆中（半衰期长达数天）具有高稳定性。制备方法，包括用于制备大单层脂质体的聚碳酸酯膜过滤器的尺寸，对囊泡大小和大小分布有主要影响。添加带电荷的脂质如二棕榈酰磷脂酰胆碱（DCP）和高达10%的不同量的聚乙二醇脂质对聚乙二醇大单层脂质体的大小和稳定性没有影响。用小鼠腹腔巨噬细胞对聚乙二醇-十六烷基磷酰胆碱脂质体与常用的十六烷基磷酰胆碱脂质体的激活效力进行了比较。十六烷基磷酰胆碱脂质体诱导小鼠腹腔巨噬细胞明显释放一氧化氮（NO）和肿瘤坏死因子（TNF），尤其是与脂多糖（LPS）协同作用时。相反，聚乙二醇脂质体在体内/体外联合激活后的作用与对照细胞相似。在用含和不含聚乙二醇脂质制备的脂质体处理小鼠（腹腔注射）后，碳墨摄取不变也证明了这些脂质体与单核吞噬细胞系统（MPS）的相互作用减少。聚乙二醇-十六烷基磷酰胆碱脂质体结合了十六烷基磷酰胆碱、脂质体和聚乙二醇包被的优点，为乳腺癌治疗提供了一种有前景的制剂。
