LIPOSOMAL CYCLOSPORINE - CHARACTERIZATION OF DRUG INCORPORATION AND INTERBILAYER EXCHANGE

A number of previous studies have examined the application of liposome s as carriers for the immunosuppressive agent cyclosporine, These stud ies, however, have generated equivocal results, particularly with rega rd to the therapeutic properties of such systems, In the present work, we have characterized cyclosporine incorporation into well defined li posomes, large unilamellar vesicles, and have examined the stability o f drug association, Contrary to some earlier reports, we show that onl y modest levels of cyclosporine can be accommodated in the liposomal m embrane and that the extent of drug incorporation is greatly reduced a s the bilayer cholesterol content is increased, Furthermore, we demons trate that cyclosporine, despite its hydrophobic character, can rapidl y exchange between vesicles, This raises the possibility that, after i .v. administration, drug migration to other blood components might neg ate the potential benefits arising from liposomal delivery, In a compa nion paper, therefore (Choice et al., Transplantation, 1995, this issu e), we have followed the pharmacokinetics and biodistribution of lipos omal cyclosporine in a study that examined the behavior of both the dr ug and the liposomal carrier.