Physical properties and tissue distribution of adriamycin encapsulated in polyethyleneglycol-coated liposomes

It is important that biodistribution and bioactivity of liposome are examined after the clarification of physical properties of this liposome. The negativity of the zeta potentials of adriamycin-encapsulating liposome with polyethylenglycol derivative (PEG-LADR) decreased with increasing NaCl concentration in lactate buffer more steeply than that of adriamycin-encapsulating liposomes (PLADR). Fixed aqueous layer thickness (FALT) around PEG-LADR as determined by the zeta potential dependence on the ionic strength, in terms of Debye Huckel parameter, was larger than that around PLADR. Time course of serum ADR concentration after the intravenous injections of the two liposomes to the rats were found to reflect the difference of FALT. The circulation time of ADR was prolonged by a simple liposome encapsulation. Further increase of the circulation time was thus correlated to FALT. In high-dose study, ADR concentration in the liver at 4 h after administration of PLADR and PEG-LADR were higher than that with ADR solution. In contrast, in lower-dose study, the reticuloendothelial system uptake of ADR was reduced by liposomalization. Thus, the difference in dose led to different distributions and there is an optimal dose at which liposomes exhibit their objective distribution. Furthermore, a correlation was indicated to exist between the circulation time of liposomes and FALT around the liposomes.