TRAPPING OF DEXTRAN-COATED COLLOIDS IN LIPOSOMES BY TRANSIENT BINDING TO AMINOPHOSPHOLIPID - PREPARATION OF FERROSOMES
TRAPPING OF DEXTRAN-COATED COLLOIDS IN LIPOSOMES BY TRANSIENT BINDING TO AMINOPHOSPHOLIPID - PREPARATION OF FERROSOMES
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DOI：
10.1016/0005-2736(94)90350-6
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发表时间：
1994-07-13
影响因子：
3.4
通讯作者：
BRADY, TJ
中科院分区：
文献类型：
--
作者：
BOGDANOV, AA;MARTIN, C;BRADY, TJ
描述了一种程序，其允许增加用葡聚糖稳定的氧化铁（MION）装载脂质体的效率。由于氧化葡聚糖与氨基磷脂的氨基基团的瞬时结合，该方法产生具有高氧化铁含量的脂质体（REV）制剂。将有机相中的含磷脂酰乙醇胺（PE）的脂质混合物（PC/DOPE/CH或SM/DOPE/CH，9：2：9摩尔比）与氧化的MION在pH 8下组合。然后通过反相蒸发获得脂质体。脂质体，直径263 +/- 89 nm，含有高达11.8 mol Fe/mol磷脂（包封率49%）。当pH值变为4.5时，10.2%的脂质体结合铁从脂质体中解离。当比较在pH 4.5和pH 8.0下孵育的脂质体制备的提取物的脂质组合物时，检测到在较低pH下孵育的脂质体提取物中相对PE含量的增加。这表明MION表面上的醛与PE之间的亚胺键解离。脂质体PE酰化的可及性通过用甲氧基聚（乙二醇）琥珀酸酯的活化酯修饰来证明。不含氨基磷脂的对照脂质体或在非氧化的MION存在下获得的含PE的脂质体对于MION包封的有效性低3.5-5倍，并且显示出广泛的聚集。
A procedure is described that allows to increase the efficiency of the loading of liposomes with dextran-stabilized iron oxides (MION). The method produces a preparation of liposomes (REVs) with high iron oxide content as a result of transient binding of oxidized dextran with aminogroups of aminophospholipids. Phosphatidylethanolamine (PE)-containing lipid mixtures (PC/DOPE/CH or SM/DOPE/CH, 9:2:9 molar ratio) in organic phase were combined with oxidized MION at pH 8. Liposomes then were obtained by reversed-phase evaporation. Liposomes, 263 +/- 89 nm in diameter, contained up to 11.8 mol Fe/mol phospholipid (encapsulation yield 49%). 10.2% of liposome-associated iron was dissociated from liposomes upon changing the pH to 4.5. When lipid compositions of extracts prepared from liposomes incubated at pH 4.5 and pH 8.0 were compared, an increase of relative PE-content in extracts of liposomes incubated at lowered pH was detected. This indicates a dissociation of imine bonds between aldehydes on the MION surface and PE. The accessibility of liposomal PE for acylation was demonstrated by modification with an activated ester of methoxy poly(ethylene glycol) succinate. Control liposomes, containing no aminophospholipid, or PE-containing liposomes obtained in the presence of non-oxidized MION, were 3.5-5-fold less effective for MION encapsulation and showed extensive aggregation.