Release profiles of recombinant human tumor necrosis factor from Ca(2+)-triggering liposome in vivo

After the administration of the recombinant human tumor necrosis factor (rHuTNF), plasma concentration could be controlled from egg yolk phosphatidylcholine (eggPC)-egg yolk phosphatidic acid (eggPA) liposome (EggPA liposome). The plasma concentration was highest after the rHuTNF solution administration. Although the concentration after the 30% EggPA liposome administration was much lower than that after the solution administration, the antitumor effect against Meth A sarcoma was equal to that of the rHuTNF solution. Non-linear elimination of rHuTNF in rat could explain these phenomena. First, to evaluate the intact absorption profile, we developed a non-linear absorption calculating program (NLAP). The calculation revealed little difference in the total absorption amounts between the solution and liposomes. The absorption rate from the liposomes was lower than that from the solution, and finally, the control of rHuTNF release from liposomes was also confirmed in vivo. These findings suggested that the sustained release of rHuTNF from liposomes maintained high drug concentration in the injected site and decreased the systemic drug concentration.