Preparation and stability of liposome encapsulated dexorubicin and mitoxantrone and their internalisation by murine peritoneal macrophages

Liposomal encapsulation of the cytotoxic drugs doxorubicin or mitoxantrone was achieved with a lipid combination of 10:1:10 DPPC/DPPG/cholesterol. Both drugs were observed, by confocal fluoroscence microscopy, to be almost entirely associated with the liposome bilayers. A method is described for loading of macrophages intraperitoneally with liposome encapsulated doxorubicin or mitoxantrone and the subsequent isolation of viable macrophages (83.5 ± 6.6%) using a separative technique based 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 located, in the case of both mitoxantrone and doxorubicin, around the periphery of the nucleus. No intracellular leakage of mitoxantrone from the liposomes after internalisation by the murine peritoneal macrophages was observed whilst some leakage was apparent for doxorubicin.