AN EPR STUDY OF LIPID VESICLES AS PARAMAGNETIC AGENT VECTORS

Paramagnetic nitroxides have been proposed as probes in electron param agnetic resonance (EPR) imaging and in clinical diagnosis. However, ni troxides are rapidly reduced in vivo to hydroxylamines, diamagnetic EP R-inactive species. Reduction occurs in blood via soluble agents such as ascorbic acid, as well as in the cells via enzymatic and non-enzyma tic endocellular systems. To prevent the reduction, a water soluble ni troxide, i.e., potassium peroxylamine disulfonate, is entrapped in rev erse phase evaporation vesicles. The loaded liposomes have a high entr apment capacity, and vesicles with the encapsulated agent are stable f or days, even at room temperature. The vesicles in vitro can almost co mpletely prevent the reduction of the entrapped nitroxide by ascorbic acid. In blood of a rat, enriched with a homogenate of rat liver prote ins, the vesicles are able to greatly prolong the life time of the nit roxide. In particular, the encapsulated nitroxide has a half-life of m ore than one hour, compared to two minutes for free nitroxide under th e same conditions. Due to these protective effects, the lipid vesicles might be useful as a delivery system for paramagnetic agents.