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Preparation and evaluation of glycyrrhetic acid‐containing microparticles as an anti‐hepatotoxic system
Author(s) -
Onishi Hiraku,
Takahashi Hiroaki,
Machida Yoshiharu
Publication year - 2005
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20042
Subject(s) - chemistry , in vivo , carbon tetrachloride , pharmacology , sonication , ethanol , pharmacokinetics , microparticle , transaminase , glycolic acid , drug , lactic acid , dosage form , chromatography , saline , biochemistry , medicine , endocrinology , organic chemistry , biology , enzyme , genetics , microbiology and biotechnology , astrobiology , bacteria
Microparticulate dosage forms for liver‐specific delivery of a liver‐protective drug, glycyrrhetic acid (GLA), were prepared and evaluated in vitro and in vivo. Poly(DL‐lactic acid‐co‐glycolic acid (7:3, mol/mol)) microparticles, produced by the combination of emulsification‐solvent evaporation and sonication and washed using the mixture of methanol‐phosphate buffered saline pH 7.4 (3:7, v/v), showed a diameter of approximately 1.0 µm, moderate drug content, and prolonged drug release, and were used for in vivo analyses. The long‐term pharmacokinetic profiles in plasma and liver were investigated after i.v. administration. The microparticles gave much higher GLA concentration in the liver than did GLA solution, and maintained plasma and liver concentrations of GLA at levels of >1 and 3 mg/mL, respectively, for at least 6 days. Furthermore, therapeutic effect against consecutive carbon tetrachloride‐induced murine hepatitis was evaluated based on the plasma level of glutamic oxalacetic transaminase (GOT) after i.v. administration. The microparticles with 10 mg GLA maintained liver‐protective effect for approximately 1 week, while the GLA solution with the same dose was scarcely effective from 3 days after the administration. These data suggest that the microparticles should be useful as a prolonged liver‐protective system. Drug Dev. Res. 66:189–199, 2006. © 2006 Wiley‐Liss, Inc.