Decreasing resistance during fast infusion of a subcutaneous tumor

High interstitial pressure limits the uptake of systemically-administered macromolecular agents. Fast infusion, which has been found to spread by convection macromolecules in the brain, was examined in a xenograft tumor system. Subcutaneous human U251 glioblastoma tumors (0.3-1.3 cm3) were infused for up to 40 minutes starting at 20 microliters/minutes while line pressure was recorded. The spread of blue dextran (molecular weight 2 x 10(6) was examined in excised tumors. Resistance to infusion decreased with time so that the infusion rate could be increased without an increase in line pressure. Blue dextran was spread up to the length of the tumor (maximum of 1.5 cm), but the spreading appeared to be asymmetric. The results suggest the pressures produced by the infusion dilated the tumor tissue, thus producing increased hydraulic conductivity. Although this produces rapid convective spread, the spread is asymmetric. Possible methods for obtaining a more uniform or controlled convective spread of macromolecular agents are discussed.