Targeted Delivery of Prostaglandin E1to Hepatocytes Using Galactosylated Liposomes

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Abstract
Prostaglandin E1 (PGE1) was incorporated in galactosylated liposomes containing cholesten-5-yloxy-N-(4-((1-imino-2-β-D-thiogalactosylethyl)amino)butyl)formamide (Gal-C4-Chol) intended for hepatocyte-selective delivery. Liposomes composed of distearoylphosphatidylcholine (DSPC)/cholesterol (Chol)/Gal-C4-Chol (60:35:5) were prepared and compared with DSPC/Chol (60:40) liposomes. After intravenous injection of [3H]-labeled PGE1 or cholesteryl hexadecyl ether (CHE) with the liposomal formulation, mice were sacrificed at a series of times, and the radioactivity in tissues was determined. Up to about 80% of [3H]CHE in galactosylated liposomes had accumulated in the liver 10 min after intravenous injection and the liver accumulation of the incorporated [3H]PGE1 was significantly higher than that in control liposomes during the entire test period. The pharmacological activity was examined in mice with fulminant hepatitis induced by peritoneal injection of carbon tetrachloride. Intravenous injection of PGE1 incorporated in DSPC/Chol/Gal-C4-Chol (60:35:5) liposomes significantly suppressed the GPT increase, whereas PGE1 (dissolved in saline) and PGE1 incorporated in DSPC/Chol (60:40) liposomes had little effect.