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Glycyrrhetic acid‐loaded microparticles: liver‐specific delivery and therapeutic potential against carbon tetrachloride‐induced hepatitis

The microparticles (MPs) of an anti‐hepatotoxic drug, glycyrrhetic acid (GLA), were prepared using poly(dl‐lactic acid‐co‐glycolic acid) as a drug carrier, and their in‐vitro properties, biodistribution and therapeutic effects were investigated. The MPs showed a particle diameter distribution of 1.0–1.4 μm and a drug content of approximately 10% (w/w). In the in‐vitro release in a mixture of methanol and phosphate‐buffered saline pH 7.4 (3:7, v/v), slow release was observed after an initial burst release of approximately 30% (w/w). After i.v. administration of MPs in normal mice, GLA was mainly distributed to the liver. After i.v. administration in normal mice, the MPs maintained a much higher liver concentration than did GLA solution, and the plasma concentration also tended to be higher for MPs than for GLA solution. As to therapeutic effect, the liver was damaged by repeated injection of carbon tetrachloride (CCl4) in mice every 48 h, and the drugs were administered intravenously as a single dose 3 h after the first injection of CCl4. At 10 mg GLA eq. kg−1, the MPs significantly suppressed the plasma level of glutamic pyruvic transaminase for at least 141 h after administration, while GLA solution did not become significantly effective within 45 h post‐administration. MPs are suggested as a possible useful system to prolong the therapeutic effect of GLA.