Targeted delivery of prostaglandin E1 to hepatocytes using galactosylated liposomes.
Prostaglandin E(1) (PGE(1) ) was incorporated in galactosylated liposomes containing cholesten-5-yloxy-N-(4-((1-imino-2-beta-D-thiogalactosyle thyl)amino)b utyl)formamide (Gal-C4-Chol) intended for hepatocyte-selective delivery. Liposomes composed of distearoylphosphatidylcholine (DSPC)/cholesterol (Chol)/Gal-C4-Chol (60&ratio;35&ratio;5) were prepared and compared with DSPC/Chol (60&ratio;40) liposomes. After intravenous injection of [(3) H]-labeled PGE(1) 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 [(3) H]CHE in galactosylated liposomes had accumulated in the liver 10 min after intravenous injection and the liver accumulation of the incorporated [(3) H]PGE(1) 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 PGE(1) incorporated in DSPC/Chol/Gal-C4-Chol (60&ratio;35&ratio;5) liposomes significantly suppressed the GPT increase, whereas PGE(1) (dissolved in saline) and PGE(1) incorporated in DSPC/Chol (60&ratio;40) liposomes had little effect.
Kawakami
S
S
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Munakata
C
C
Fumoto
S
S
Yamashita
F
F
Hashida
M
M
D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000527:Alprostadil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D004337:Drug Carriers; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics
D004337:Drug Carriers; D008081:Liposomes; D010975:Platelet Aggregation Inhibitors; D002251:Carbon Tetrachloride; D000410:Alanine Transaminase; D000527:Alprostadil