LOADING OF DOXORUBICIN INTO LIPOSOMES BY FORMING MN2-DRUG COMPLEXES()

A new procedure for loading doxorubicin into large unilamellar vesicle s (LUVs) is characterized. It is shown that doxorubicin can be loaded into LUVs composed of sphingomyelin/cholesterol (55:45 mole/mole) in r esponse to a transmembrane MnSO4 gradient in the absence of a transmem brane pH gradient. Complex formation between doxorubicin and Mn2+ is f ound to be a driving force for doxorubicin uptake. Uptake levels appro aching 100% can be achieved up to a drug-to-lipid molar ratio of 0.5 u tilizing an encapsulated MnSO4 concentration of 0.30 M, In vitro leaka ge assays show excellent retention properties over a 24 h period. The possible advantages of a liposomal formulation of doxorubicin loaded i n response to entrapped MnSO4 are discussed. (C) 1998 Elsevier Science B.V. All rights reserved.