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- W2943622434 abstract "1395 Liposomes are recognized as one of the useful drug carrier, but have many problems in order to clinical application. Liposomes, bond peculiarly with serum protein (opsonization), are taken up by reticuloendothelial system (RES) cells in the liver and spleen. This is one of the principal causes that is reduced the effectiveness of liposomes as a drug carrier if its purpose is long-term circulation in the blood or targeting to tissues except the RES. It was known that polyethyleneglycol (PEG) modification of the liposome surface produced formation of fixed aqueous layer around the liposomes by interaction between the PEG-polymer and water molecule, and prevented the attraction of opsonins. Namely, PEG-modified liposomes are able to escape trapping by the cells of RES, and have a prolonged circulation time. In this study, the effects of different anchor with same PEG molecular weight on the cell uptake and cytotoxicity of mixed PEG-modified liposomal doxorubicin (DOX) were examined. In PEG-distearoylglycerol (PEG-DSG) modification of liposome, a fixed aqueous layer thickness (FALT) increased with the increase in a molecular weight. Similarly, PEG-cholesterol (PEG-CHO) modification was increased FALT with the increase in a molecular weight, too. FALT of liposome with modification by a mixture of PEG2000 and PEG with a short chain increased, compared to that of the single PEG2000-modified liposome. Mix PEG-modification of liposome by different anchor (PEG2000-(DSG:CHO=1:1)- modified liposome) led to increase in FALT, compared to that of each single PEG-modification. The uptake of DOX into Ehrlich ascites carcinoma cells in PEG-CHO modified group is higher than other liposomes. The effect of PEG-modification on DOX uptake in tumor cells is shown and this order was PEG2000-(DSG:CHO=1:1) = PEG2000-CHO > PEG2000-DSG > unmodified liposomal DOX. This result suggested that PEG-CHO had higher affinity on tumor cells. The effect of PEG-modification on IC50 by DOX reflected in cell uptake of each liposome. Namely, this order was PEG2000-DSG > PEG2000-CHO > PEG2000-(DSG:CHO=1:1). Thus, mixed PEG-modified liposomes with PEG-DSG and PEG-CHO were suggested to be effective to increase cytotoxicity. In conclusion, it was confirmed that mix-modified liposomes by PEG-lipid with different anchor were superior." @default.
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- W2943622434 date "2005-05-01" @default.
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- W2943622434 title "Effect of mix polyethyleneglycol modification contained doxorubicin on cell uptake and cytotoxicity" @default.
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