Tumor accumulation of novel RES-avoiding liposomes

Abstract

For passive targeting of liposomes to tumor tissues, we earlier developed reticuloendotheelial system (RES)-avoiding liposomes modified with a uronic acid derivative, palmityl- d-glucuronide (PGlcUA) (Namba, Y., Sakakibara, T., Masada, M., Ito, F. and Oku, N. (1990) Chem. Pharm. Bull. 38, 1663–1666). In this present study, we examined the blood clearance and biodistribution of PGlcUA-liposomes (dipalmitoylphoshatidylcholine/cholesterol/PGlcUA = 40: 40: 20 as a molar ratio ) in normal and tumor-bearing mice. Liposomes containing dipalmitoylphophatidylglycerol (DPPG) instead of PGlcUA was also examined as a control. When [ 3H]inulin-encapsulated PGlcUA-liposomes and DPPG-liposomes were intravenously injected into normal mice, approx. 50% of the 3H radioactivity was recovered from the liver, the bulk of RES, at 12 h after administration of DPPG-liposomes, while only approx. 20% of it was found there when PGlcUA-liposomes were administered. Radioactivity remaining in the plasma at 12 h after injection was 5-fold higher when PGlcUA-liposomes were injected than when DPPG-liposomes were used. Biodistribution of liposomes in tumor-bearing mice was also examined. Mice were inoculated with 10 7 S180 cells into the hind leg. After 1 week, liposomes were injected. Radioactivity of [ 3H]inulin originally encapsulated in the PGlcUA-liposomes accumulated in the tumor to an extent 3–4-fold higher than that of the marker in DPPG-liposomes. Liver/tumor ration of the radioactivity was 12 for DPPG-liposomes and only 2 for PGlcUA-liposomes. This latter value is the lowest of various liposome formulations ever reported.