PREPARATION AND STABILITY OF LIPOSOME-ENCAPSULATED DOXORUBICIN AND MITOXANTRONE AND THEIR INTERNALIZATION BY MURINE PERITONEAL-MACROPHAGES

Liposomal encapsulation of the cytotoxic drugs doxorubicin or mitoxant rone was achieved with a lipid combination of 10:1:10 DPPC/DPPG/choles terol. Both drugs were observed, by confocal fluorescence microscopy, to be almost entirely associated with the liposome bilayers. A method is described for loading of macrophages intraperitoneally with liposom e encapsulated doxorubicin or mitoxantrone and the subsequent isolatio n of viable macrophages (83.5 +/- 6.6%) using a separative technique b ased on Ficoll and Percoll. Confocal microscopy also revealed that the intact liposomes were internalised in macrophages and that liposomal drug was located in phagosomes. By comparison the free drug was locate d, in the case of both mitoxantrone and doxorubicin, around the periph ery of the nucleus. No intracellular leakage of mitoxantrone from the liposomes after internalisation by the murine peritoneal macrophages w as observed whilst some leakage was apparent for doxorubicin.