Abstract
Long-circulating liposomes containing amphipathic polyethyleneglycol (PEG) have been tested for their utility as enhanced delivery system of doxorubicin(DXR) to the solid tumor. Inclusion of PEG to the small unilamellar liposomes(SUV, DSPC/CH (1 : 1, m/m), 120 nm in mean diameter) encapsulating DXR showed the increased blood level and the decreased RES uptake of SUV, and resulted in high accumulation of SUV into the colon 26 solid tumor site. Reflecting to these behavior of PEG-SUV, DXR concentration in tumor tissue was significantly increased, and effective tumor-growth retardation and increased survival time were observed. These data indicate that since the capillary permeability of the endothelial barrier in newly vascularized tumors is significantly greater than that of normal organs, SUV with prolonged circulation time could predominantly pass through leaky endothelium into tumor area by passive convective transport. DXR encapsulated in long-circulating liposomes will be much more effective for cancer chemotherapy than either the usual liposomal DXR or free DXR.
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