Targeted and sustained drug delivery using PEGylated galactosylated liposomes

To achieve a sustained and targeted delivery of liposomes to liver parenchymal cells (PC), we modified distearoyl-L-phosphatidylcholine (DSPC)/cholesterol (Chol) (60:40) (DSPC/Chol) liposomes with a galactosylated cholesterol derivative (Gal-C4-Chol), and polysorbate (Tween) 20 or 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-polyethylene glycol (PEG,-DSPE). After intravenous injection, DSPC/Chol/Gal-C4-Chol (60:35:5) (Gal) liposomes were rapidly eliminated from the blood circulation and mostly recovered in the liver. The blood elimination of DSPC/Chol/Gal-C4-Chol/Tween 20 (55:35:5:5) (Tween 20-Gal) liposomes was slightly reduced as compared to Gal-liposomes. In contrast, a significant reduction in the blood elimination was observed with DSPC/Chol/Gal-C4-Chol/PEG(2000)-DSPE (59:35:5:1) (PEG(2000)-Gal) liposomes. Hepatic uptake of DSPC/Chol/Gal-C4-Chol/PEG(350)-DSPE (59:35:5:1) (PEG(350)-Gal) liposomes was intermediate between PEG(2000)-Gal-liposomes and Tween 20-Gal-liposomes. The uptake of PEG(350)-Gal-liposomes by liver PC was 7.7-fold higher than that by non-parenchymal cells (NPC). These results suggest that PEG(350)-DSPE can control the delivery rate of Gal-liposomes to liver PC without losing its targeting capability. (C) 2003 Elsevier B.V. All rights reserved.