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• W2062655552 abstract "Incorporation of N-(omega-carboxy)acylamido-phosphatidylethanolamines (-PEs) into large unilamellar vesicles (LUVs) of L-alpha-distearoylphosphatidylcholine (DSPC) was found to dramatically increase the in vivo liposomal circulation lifetime in rats, reaching a maximal effect at 10 mol.% of the total phospholipid. Neither pure DSPC liposomes nor those with the longest circulating derivative, N-glutaryl-dipalmitoylphosphatidylethanolamine (-DPPE), were found to significantly bind complement from serum. Therefore, the relatively short circulation time of pure DSPC liposomes did not appear to be related to greater complement opsonization leading to uptake by the reticuloendothelial system. However, N-(omega-carboxy)acylamido-PEs were particularly efficient inhibitors of a limited aggregation detected for pure DSPC liposomes. The aggregation tendency of DSPC liposomes incorporating various structural analogs of N-glutaryl-DPPE correlated inversely with the circulation lifetimes. Therefore, it is concluded that such PE derivatives enhance the circulation time by preventing liposomal aggregation and avoiding a poorly understood mechanism of clearance that is dependent on size but is independent of complement opsonization. At high concentrations of N-glutaryl-DPPE (above 10 mol.%), the liposomes exhibited strong complement opsonization and were cleared from circulation rapidly, as were other highly negatively charged liposomes. These data demonstrate that both the lack of opsonization and the lack of a tendency to aggregate are required for long circulation. Liposomal disaggregation via N-(omega-carboxy)acylamido-PEs yields a new class of large unilamellar DSPC liposomes with circulation lifetimes that are comparable to those of sterically stabilized liposomes." @default.
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• W2062655552 date "1997-10-01" @default.
• W2062655552 modified "2023-09-25" @default.
• W2062655552 title "Enhancement of the in vivo circulation lifetime of l-α-distearoylphosphatidylcholine liposomes: importance of liposomal aggregation versus complement opsonization" @default.
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• W2062655552 doi "https://doi.org/10.1016/s0005-2736(97)00129-6" @default.
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