Although small, 100-nm
liposomes are known to selectively accumulate in solid
tumors, the individual contributions of
liposome influx and egress rates are not well understood. The aim of this work was to determine influx and efflux kinetics for 100-nm,
1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/
cholesterol (Chol)
liposomes by inducing aggregate formation of biotinylated
liposomes upon administering
avidin. Injecting 50 microg of
neutravidin intravenously to mice that had previously been administered 100 mg/kg DPSC/Chol
liposomes containing 0.5 mol%
biotin-conjugated
lipid resulted in >90% elimination of the
liposomes from plasma within 1 h. This rapid removal by the reticuloendothelial system (RES) permitted the determination of the
tumor efflux kinetics due to negligible
tumor influx after
neutravidin injection. The
tumor efflux rate constant (k(-1)) was determined to be 0.041 h(-1) when
neutravidin was injected 4 h after
liposome injection. This allowed the determination of the
tumor influx rate constant (k(1)), which under these conditions was 0.022 h(-1). Therefore, DSPC/Chol liposomal accumulation, in LS180 solid
tumors, is dictated primarily by plasma
liposome concentrations and
liposome egress is comparable or slightly faster than influx into the
tumors. This method is applicable for a wide range of
lipid doses, and can be used to characterize influx and efflux parameters at different time points after accumulation. The application, therefore, has the potential to be used to fully characterize the impact of different
liposome parameters such as
lipid composition, steric stabilization, size and dose on
tumor accumulation kinetics.