Targeted Delivery of Prostaglandin E1to Hepatocytes Using Galactosylated Liposomes

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.