Preparation, antitumor activity in mice, pharmacokinetics and tissue distribution in rats of di‐n‐butyl‐di‐(4‐chlorobenzohydroxamato)tin(IV) liposome
Di-n-butyl-di-(4-chlorobenzohydroxamato)tin(IV) (DBDCT) is an antitumor compound with high activity and relatively low bioavailability. In order to improve the pharmacokinetic characteristics and raise its therapeutic index, a liposome of DBDCT (DBDCT-L) was prepared for the first time. A study of the pharmacokinetics and tissue distribution after intravenous administration of DBDCT-L compared with free DBDCT to rats was investigated. DBDCT-L showed a slower clearance, increased half-time and a larger AUC value than those of free DBDCT, which demonstrated that DBDCT-L could significantly alter the tissue distribution pattern of DBDCT in rats. The highest concentration distribution for DBDCT-L was detected in liver, which may be associated with the enhanced antitumor activity in vivo against hepatocellular carcinoma H22 and possible target release of the compound. Acute toxicity assay showed that the LD50 value of DBDCT-L was higher than that of free DBDCT. Further in vivo antitumor test showed that DBDCT-L displayed higher antitumor activity against the hepatocellular carcinoma H22 than free DBDCT, indicating that the liposome could prolong the action time of DBDCT in the system circulation, change its distribution in rats, reduce acute toxicity and finally increase antitumor activity. Copyright © 2014 John Wiley & Sons, Ltd.