Biological characterization of L-asparaginase liposomal formulations.

The biological properties of preselected liposomal formulations of L-asparaginase (L-ASNase) were studied. Pharmacokinetics studies showed that encapsulation in large liposomes (sDRV; median diameter 1,249 nm) decreased the circulation time of the enzyme, whereas encapsulation in small liposomes (VET: median diameter 158-180 nm) prolonged it by a factor of up to 10. Liposome encapsulation in either VET or sDRV prevents the induction of anti-asparaginase antibodies and mitigates the anaphylatic reaction, as no death occurred in animals presensitized and challenged with liposomal formulation, in contrast to animals treated with the free enzyme. The antitumor activity was also enhanced by liposome encapsulation. The survival of animals bearing P1534 tumors was prolonged by a factor of 2 after treatment with selected liposomal formulations as compared with free enzyme.