Glucuronate-Modified Liposomes with Prolonged Circulation Time

Abstract

For the purpose of obtaining liposomes with long circulation time in blood, we synthesized 1-0-palmityl-D-glucuronic acid (PG1cUA) and incorporated it into the liposomal membranes. The clearance of the PG1cUA—liposomes composed of dipalmitoylphosphatidylcholine (DPPC), cholesterol, and PG1cUA (40 as a molar ratio) from blood and their tissue distribution were compared with those of dipalmitoylphosphatidylglycerol (DPPG)—liposomes (DPPC/cholesterol/DPPG = 40 When [H]inulin-loaded PG1cUA—liposomes and DPPG—liposomes were intravenously injected into rats, the half-life of the PG1cUA—liposomes in the blood appeared to be 1.7-fold longer than that of DPPG—liposomes. Radioactivities present in plasma and various tissues were measured 22 h after administration of these liposomes, and radioactivity remaining in the plasma was 25-fold greater when PG1cUA—liposomes were injected. The distribution pattern of [3H]inulin in PG1cUA—liposomes was similar to that in DPPG—liposomes. The radioactivity recovered in urine was 25% lower in rats treated with PG1cUA—liposomes than in those treated with DPPG—liposomes. Since both PG1cUA— and DPPG—liposomes exhibited similar size distribution and ζ-potential glucuronic acid, rather than negative charge, on the liposomal surface appears to endow liposomes with a longer circulation time in the bloodstream. © 1990, The Pharmaceutical Society of Japan. All rights reserved.