Abstract
It is known that polyethyleneglycol (PEG) modification of the liposome surface leads to the formation of a fixed aqueous layer around the liposomes due to interaction between the PEG polymer and water molecules, which prevents the attraction of opsonins. When a combination of PEG-distearolyglycerol (PEG-DSG) whose characteristics are remarkably different is used, interaction between molecules occurs, leading to increased fixed aqueous layer thickness (FALT). From this speculation, we studied the effect of both modification of PEG900-DSG and PEG2000-DSG modified liposome on FALT, cell uptake and biodistribution. The FALT of mixed PEG modified liposome increased, compared to that of each single PEG modified liposome. In this mixed modification, maximum FALT was shown at liposome modified by added PEG-2000:PEG-900=2:1. This most suitable additional ratio was equal to actual incorporated ratio. On the other hand, cell uptake of mixed modified liposome containing doxorubicin (DOX) was similar with that of PEG2000 modified liposome. Furthermore, mixed PEG modification of liposome was tendency to increase cytotoxicity, compared to that of other modifications. After DOX contained liposome treatment, DOX distribution in the tumor and antitumor activity of DOX increase by mixed PEG modification. In conclusion, it was suggested that mixed PEG liposome (PEG-2000:PEG-900=2:1) was useful for cancer chemotherapy.
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