Temperature-Dependent Drug Release from Large Unilamellar Liposomes

Abstract

The drug-release properties of large unilamellar liposomes were measured at temperatures near the lipid's phase-transition temperature. The liposomes were formed from a mixture of dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylglycerol (4:1 by weight) by the reverse-phase evaporation process. These liposomes captured 25-35% of the radiolabeled anticancer drug cytosine [³H]-1-β-arabinofuranoside in their aqueous compartment. They were stable in serum below the lipid's phase-transition temperature of 41°C. Complete drug release occurred within seconds after the liposomes reached a temperature of 43°C in serum. Addition of cholesterol or phosphatidylglycerol to the liposomal membrane reduced the drug-release temperature and broadened the range of drug release. These results show that suspensions of large unilamellar liposomes can be made to encapsulate a therapeutically useful quantity of drug that is rapidly and completely released at 43°C in serum.