LIPOSOMAL CYCLOSPORINE - COMPARISON OF DRUG LIPID CARRIER PHARMACOKINETICS AND BIODISTRIBUTION

In a preceding paper (Ouyang et al., 1995, this issue), we have charac terized cyclosporine incorporation into well-defined liposomal systems , large unilamellar vesicles. This study demonstrated that only modest drug levels could be accomodated within the membrane, particularly fo r cholesterol-containing Liposomes, and that rapid drug exchange could occur between vesicles. This raised the possibility that following in travenous administration, drug migration to other blood components mig ht negate the potential benefits arising from liposomal delivery. We h ave, therefore, examined the pharmacokinetics and biodistribution of b oth cyclosporine and its Liposomal carrier. We show that whereas Lipos omes, as expected, are only slowly cleared from the blood, redistribut ion of cyclosporine occurs much more rapidly. Further we have shown th at Liposomal loss of cyclosporine in blood results fi om drug migratio n to the lipoproteins and, to a lesser extent, the erythrocytes. As a result, while Liposomes accumulate preferentially in organs of the ret iculoendothelial system after intravenous administration, tissue cyclo sporine levels, in general, do not reflect the distribution profile ob tained for the liposomal carrier.