Preparation and evaluation of temperature-sensitive liposomes containing doxorubicin(DXR) by pH gradient method

Temperature-sensitive liposomes containing dox-orubicin(DXR-TSL (pH)) composed of DPPC (Tc = 41°C)/DSPC (Tc = 54°C) (9 : 1 in molar ratio) were prepared by pH gradient method and evaluated concerning tumor uptake of DXR. Colon 26 tumor cells were inoculated in hind foot of BALB/c mice and local hyperthermia (42°C, 20 min) was done at tumor site. The pH gradient method was employed to raise the encapsulation rate of DXR into temperature sensitive liposomes. This preparation resulted in the remarkably high encapsulation rate with 98%. The tumor uptake of DXR with the combination of DXR-TSL(pH) and the local hyperthermia were 3 times greater than those of free DXR. The higher accumulation of DXR in liver and spleen was obser ved. In these accumulation, the distribution of liposome rather than released DXR was contributed mainly. Present data indicated that DXR-TSL(pH) have some advantages for the antitumor effect, since DXR content per liposome is high and the controlled release of DXR from liposomes with hyperthermia is possible.