LIPOSOMES FOR THE SUSTAINED DRUG RELEASE INVIVO
LIPOSOMES FOR THE SUSTAINED DRUG RELEASE INVIVO
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DOI：
10.1016/0005-2736(90)90440-y
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发表时间：
1990-11-02
期刊：
影响因子：
--
通讯作者：
CEVC, G
中科院分区：
文献类型：
--
作者：
BLUME, G;CEVC, G
介绍了适合于药物体内缓释的新型药物载体。它们由中等大小的紧凑磷脂囊泡组成，具有一个或多至几个脂质双层，这些脂质双层用少量大头磷脂空间稳定。作为一个例子，磷脂酰胆碱（PC）脂质体铸造高达10 mmol%的磷脂酰乙醇胺与共价连接的聚乙二醇5000头基（PE-PEG）进行了讨论。这种囊泡在小鼠中静脉内给药后表现出非常长的循环时间;在前24小时内，相对于纯磷脂酰胆碱脂质体的改善超过8000%，此时几乎25%的所施用的PE-PEG脂质体仍在循环中。这种优势是减少的噬菌体载体的吞噬作用的结果，如在流式细胞术实验中用血液单核细胞的体外测定所示。例如，在人血浆中与THP-1单核细胞孵育6小时后，标准二硬脂酰磷脂酰胆碱（DSPC）和含有10%二硬脂酰磷脂酰乙醇胺-PEG的新型脂质体的摄取之间的差异为1000%。具有2.5 mol% DSPE-PEG的囊泡也通过吞噬作用相对缓慢地被摄取。但后者囊泡，而且，保留了大部分的封闭模型药物羧基荧光素后，在血浆中孵育。包封物质从这种DSPE-PEG脂质体中的渗透速率低于2.4%/h。这比纯DSPC脂质体低约两倍;在这方面，具有较高PE-PEG含量的囊泡较差。新开发的脂质体的长循环时间和高保留为将来作为用于体内治疗应用的稳定药物载体的全身使用开辟了途径。
New lipidic carriers suitable for the sustained drug release in vivo are presented. They consist of middle sized, compact phospholipid vesicles with one or up to few lipid bilayers which are sterically stabilized with a small amount of large-head phospholipids. As an example, phosphatidylcholine (PC) liposomes casted with up to 10 mmol% of phosphatidylethanolamine with a covalently attached polyethyleneglycol 5000 headgroup (PE-PEG) are discussed. Such vesicles exhibit a very long circulation time after an i.v. administration in mice; the improvement over pure phosphatidylcholine liposomes within the first 24 h exceeds 8000%, at this point nearly 25% of the applied PE-PEG liposomes being still in the circulation. This advantage is a consequence of reduced phagocytosis of the lipidic carriers, as shown by an in vitro assay with blood monocyte cells in the flow cytometric experiments. For example, after 6 h incubation with THP-1 monocyte cells in human plasma the difference between the uptake of standard distearoylphosphatidylcholine (DSPC) and novel liposomes containing 10% distearoylphosphatidylethanolamine-PEG is by 1000%. Vesicles with 2.5 mol% DSPE-PEG are also taken-up via phagocytosis relatively slowly. But the latter vesicles, moreover, retain most of the enclosed model-drug carboxyfluorescein after an incubation in plasma. The rate of permeation of the encapsulated substance from such DSPE-PEG liposomes is below 2.4% per h. This is by approximately a factor of two less than for pure DSPC liposomes; vesicles with a higher PE-PEG content are inferior in this respect. Long circulation time and high retention of the newly developed liposomes open up ways for the future systemic use as such stabilized drug carriers for the therapeutic applications in vivo.