Abstract
We prepared temperature-sensitive liposomes containing doxorubicin (DXR) which release the drug at 42°C required for local hyperthermia.The liposomes were prepared by mixing dipalmitoylphosphatidylcholine (DPPC) with distearoylphosphatidylcholine (DSPC) and cholesterol, according to the procedure of the reverse-phase evaporation method.The drug-releasing properties of the large unilamellar liposomes were measured at 36 to 42°C around the phase transition temperature of the liposomal lipids.
The addition of cholesterol reduced the membrane permeability of the liposomes and cornpletely eliminated DXR release at 50 mol%.The liposomes composed of DPPC alone released approximately 80% of DXR at 39°C.DPPC liposomes containing 20 mol% DSPC, however, showed a sharp increase in DXR release between 40°C and 42°C. At 42°C, the level of DXR release was approximately 90%.These results indicated that the lipid composition of DPPC/ DSPC=4/1 (molar ratio) was optimum for temperature-sensitive DXR release.
