Liposomal cyclosporine. Characterization of drug incorporation and interbilayer exchange

Abstract

A number of previous studies have examined the application of liposomes as carriers for the immunosuppressive agent cyclosporine. These studies, however, have generated equivocal results, particularly with regard to the therapeutic properties of such systems. In the present work, we have characterized cyclosporine incorporation into well defined liposomes, large unilamellar vesicles, and have examined the stability of drug association. Contrary to some earlier reports, we show that only modest levels of cyclosporine can be accommodated in the liposomal membrane and that the extent of drug incorporation is greatly reduced as the bilayer cholesterol content is increased. Furthermore, we demonstrate that cyclosporine, despite its hydrophobic character, can rapidly exchange between vesicles. This raises the possibility that, after i.v. administration, drug migration to other blood components might negate the potential benefits arising from liposomal delivery. In a companion paper, therefore (Choice et al., Transplantation, 1995, this issue), we have followed the pharmacokinetics and biodistribution of liposomal cyclosporine in a study that examined the behavior of both the drug and the liposomal carrier.