Document Detail


A combination of liposomal sunitinib plus liposomal irinotecan and liposome co-loaded with two drugs enhanced antitumor activity in PC12-bearing mouse.
MedLine Citation:
PMID:  23050928     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Pheochromocytomas are highly angiogenic neuroendocrine tumors. The side effects of treatment with cytotoxic agents frequently outweigh the benefits. Neuroendocrine tumors are highly angiogenic, dependent on vascular endothelial growth factor and receptor (VEGFR) activation. Sunitinib has antitumor and antiangiogenic activities that target VEGFRs. We investigated the antitumor activity of liposomal sunitinib and irinotecan alone and in combination. Liposomal sunitinib and irinotecan, and liposomes co-loaded with both drugs were prepared, and antitumor activity and biodistribution were examined in nude mice bearing PC12 tumors. Liposomal sunitinib increased in life span (ILS, 14.3%) compared with free sunitinib (-17.1% ILS) with moderate tumor growth suppression, whereas liposomal irinotecan suppressed tumor growth significantly without a survival benefit compared with free irinotecan (-21.7 and -13.3% ILSs, respectively). The combination of liposomal sunitinib plus liposomal irinotecan, and liposomes co-loaded with both drugs, induced significant inhibition of tumor growth and increased life-span more than the combination of free drugs. Accumulation of irinotecan in tumors by the combination of the two liposomal drugs and liposomes co-loaded with both drugs was significantly increased compared with the combination of free drugs. This study provides novel formulations of sunitinib and irinotecan in combination for the treatment of pheochromocytoma.
Authors:
Yoshie Maitani; Hiroshi Saito; Yuki Seishi; Yuko Iwase; Takayasu Yamauchi; Kimio Higashiyama; Takashi Sugino
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-11
Journal Detail:
Title:  Journal of drug targeting     Volume:  -     ISSN:  1029-2330     ISO Abbreviation:  J Drug Target     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9312476     Medline TA:  J Drug Target     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Institute of Medicinal Chemistry, Hoshi University , Tokyo , Japan.
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