Temperature-dependent drug release from large unilamellar liposomes.
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-beta-arabinofuranoside in their aqueous compartment. They were stable in serum below the lipid's phase-transition temperature of 41 degrees C. Complete drug release occurred within seconds after the liposomes reached a temperature of 43 degrees 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 degrees C in serum.
D001769:Blood; D002021:Buffers; D002784:Cholesterol / Q000494:pharmacology; D003561:Cytarabine / Q000008:administration & dosage; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D010715:Phosphatidylglycerols / Q000008:administration & dosage; D011663:Pulmonary Surfactants / Q000008:administration & dosage; D013696:Temperature
D002021:Buffers; D008081:Liposomes; D004364:Pharmaceutical Preparations; D010715:Phosphatidylglycerols; D011663:Pulmonary Surfactants; D003561:Cytarabine; D002784:Cholesterol; C030345:1,2-dipalmitoylphosphatidylglycerol