Magnetic Field-Induced Drug Permeability in Liposome Vesicles

Abstract

Liposome vesicles maintained in a uniform static magnetic field release a chemotherapeutic drug (ARA-C, MW = 243) at temperatures approaching the phase-transition region where these liposomes are not normally leaky. Drug release is rapid, and a maximum difference between treated and unexposed liposomes of 30% of the total maximal release of ARA-C was observed within 1 min in a magnetic field. Dose-effect studies conducted between 0.01 and 7.5 T (1 T = 10(4) G) reveal that this permeability effect has a sigmoidal dependence on magnetic flux density. The ED50 is 15 mT, with a 95% confidence interval of 6.50-34.9 mT. Magnetic field exposures were conducted using a superconducting magnet with the liposomes maintained at +/- 0.08 degrees C. For comparison, samarium-cobalt permanent magnets induced a comparable drug release at 0.4 T. These results indicate that a static magnetic field of 10 mT or greater can increase passive transport in phospholipid membrane bilayers maintained at or near their membrane phase-transition temperature. Lipid clustering which occurs at prephase-transition temperatures may predispose phospholipid domains to diamagnetic orientation in a magnetic field and thereby facilitate drug release.