Loading of doxorubicin into liposomes by forming Mn2+-drug complexes.
A new procedure for loading doxorubicin into large unilamellar vesicles (LUVs) is characterized. It is shown that doxorubicin can be loaded into LUVs composed of sphingomyelin/cholesterol (55:45 mole/mole) in response to a transmembrane MnSO4 gradient in the absence of a transmembrane pH gradient. Complex formation between doxorubicin and Mn2+ is found to be a driving force for doxorubicin uptake. Uptake levels approaching 100% can be achieved up to a drug-to-lipid molar ratio of 0.5 utilizing an encapsulated MnSO4 concentration of 0.30 M. In vitro leakage assays show excellent retention properties over a 24 h period. The possible advantages of a liposomal formulation of doxorubicin loaded in response to entrapped MnSO4 are discussed.
Cheung
B C
BC
University of British Columbia, Department of Biochemistry and Molecular Biology, 2146 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
Sun
T H
TH
Leenhouts
J M
JM
Cullis
P R
PR
D002784:Cholesterol; D004317:Doxorubicin / Q000737:chemistry*; D004337:Drug Carriers; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry*; D008345:Manganese / Q000032:analysis / Q000737:chemistry*; D017895:Manganese Compounds; D013109:Sphingomyelins; D013431:Sulfates; D013696:Temperature
D004337:Drug Carriers; D008081:Liposomes; D017895:Manganese Compounds; D013109:Sphingomyelins; D013431:Sulfates; D008345:Manganese; D004317:Doxorubicin; D002784:Cholesterol; C039798:manganese sulfate