Premium
Preparation, antitumor activity in mice, pharmacokinetics and tissue distribution in rats of di‐n‐butyl‐di‐(4‐chlorobenzohydroxamato)tin(IV) liposome
Author(s) -
Ge Rui,
Wang YiJie,
Tang Li,
Cheng JingMin,
Han LingGe,
Li YunLan,
Li QingShan
Publication year - 2014
Publication title -
applied organometallic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.53
H-Index - 71
eISSN - 1099-0739
pISSN - 0268-2605
DOI - 10.1002/aoc.3112
Subject(s) - pharmacokinetics , chemistry , in vivo , bioavailability , pharmacology , liposome , distribution (mathematics) , toxicity , hepatocellular carcinoma , acute toxicity , in vitro , therapeutic index , tissue distribution , biochemistry , medicine , drug , mathematics , organic chemistry , biology , mathematical analysis , microbiology and biotechnology
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 H 22 and possible target release of the compound. Acute toxicity assay showed that the LD 50 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 H 22 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.