Distribution and pharmacology of intravenous ^99mTc-labeled multilamellar liposomes in rats and mice

The use of liposomes for the delivery of macrophage activators offers a new approach for the selective targeting of antitumor therapy. We have investigated the distribution, retention, and pharmacology of multilamellar liposomes (phosphatidylserine (PS): phosphatidylcholine (PC) 3:7) on i.v. injection in normal rats. Sprague-Dawley rats were injected with doses varying from 300 to 1000 mg/kg of ^99mTc-liposomes. The organ distribution of doses ranging from 300 to 500 mg/kg showed 45% mean uptake by liver, 25% by spleen, and 4% by lung. At higher doses of 800-1000 mg/kg, uptake in the lung increased significantly to 9 ± 3%. Whole body retention at 24 h after i.v. injection in Hale Stoner mice was 70%. The blood disappearance curve was biphasic and compared with the free isotope, a decrease was observed in the initial a phase t _{1 2} while the terminal phase t _{1 2} increased by 100%. These data suggest that encapsulation prolongs the initial distribution to the peripheral compartments and that higher doses may increase uptake by organs other than the liver.