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To fully understand the potential and limitations of drug-laden liposomes in therapy, it is necessary to have information available on the behaviour of both drug and liposome in the body after administration. For two cytostatics (doxorubicin and cisplatin) the effect of liposome encapsulation on the therapeutic index was studied in tumor-bearing rats. Data were collected on the fate of liposome and drug in the rats. Analysis of these data provided a possible explanation for the observation that liposome encapsulation increased the therapeutic index for doxorubicin, but not for cisplatin. In the second part of this article the beneficial effect of liposome encapsulation of chloroquine (CQ) on the treatment and prophylaxis of murine malaria is demonstrated. This effect could be ascribed to sustained release of CQ from the intraperitoneally injected liposomes. Finally, examples of successful drug targeting with CQ containing immunoliposomes, or successive administration of antibodies and CQ containing liposomes, in a murine malaria model are presented.

An overview of the literature concerning in vivo studies with immunoliposomes is presented. The design of immunoliposomes, their fate in vivo in the light of physiological constraints as well as potential applications are discussed. It appears that the therapeutic utility is restricted to a limited number of applications. General rules for a successful deployment of immunoliposomes are slowly emerging.

Immunoliposomes were made by covalently linking Fab' fragments (from rabbit antimouse erythrocyte IgG) to reverse-phase evaporation vesicles (REV) via maleimido-4-(p-phenylbutyrate) phosphatidylethanolamine (MPB-PE) as anchor molecule. These immunoliposomes were characterized in terms of size, charge, stability and antigen binding capacity. The effect of the liposomal Fab' density on the interaction with the target cell was studied. Two isolation methods were tested to separate free Fab' from liposomally bound Fab'. The necessity of deactivation of remaining reactive sites with dithiothreitol preincubation to increase the specificity of immunoliposome target cell interactions was demonstrated.