Tumor accumulation of novel RES-avoiding liposomes.
For passive targeting of liposomes to tumor tissues, we earlier developed reticuloendothelial 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 (dipalmitoylphosphatidylcholine/cholesterol/PGlcUA = 40:40:20 as a molar ratio) in normal and tumor-bearing mice. Liposomes containing dipalmitoylphosphatidylglycerol (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 ratio 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.
Oku
N
N
Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Namba
Y
Y
Okada
S
S
D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D005965:Glucuronates / Q000493:pharmacokinetics; D007700:Kinetics; D008081:Liposomes / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D012157:Mononuclear Phagocyte System / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000378:metabolism*; D010715:Phosphatidylglycerols / Q000378:metabolism / Q000493:pharmacokinetics
D005965:Glucuronates; D008081:Liposomes; D010715:Phosphatidylglycerols; C065782:1-O-palmitylglucuronic acid; D002784:Cholesterol; C030345:1,2-dipalmitoylphosphatidylglycerol