Document Detail


Co-delivery of daunomycin and oxaliplatin by biodegradable polymers for safer and more efficacious combination therapy.
MedLine Citation:
PMID:  22698937     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
An oxaliplatin pro-drug (Oxa(IV)-COOH) with an axial carboxyl group was synthesized and conjugated to biodegradable polymers with pendant hydroxyl groups to prepare polymer-Oxa(IV) conjugates. A hydrophobic anthracycline-based drug, daunorubicin (DRB) was conjugated to similar biodegradable polymers with carboxyl groups to synthesize polymer-DRB conjugates. The two drug conjugates have the similar polymer backbone and are amphiphilic, thus they can co-assemble into composite micelles. In the composite micelles, the polymer-Oxa(IV) conjugates can release clinically widely used water soluble anticancer drug oxaliplatin (Oxa(II)) upon reduction, while polymer-DRB conjugate is thought to release DRB via acid hydrolysis in the cancer cells. In this way, combination of the hydrophilic platinum drug Oxa(II) and hydrophobic drug DRB can be realized by delivering them in one platform. Moreover, the composite micelles showed reduced systematic toxicity and greater synergistic effect than combination of small molecules of the two anticancer drugs both in vitro and in vivo, thus this polymer based combination therapy can be useful in future clinic application.
Authors:
Haihua Xiao; Wenliang Li; Ruogu Qi; Lesan Yan; Rui Wang; Shi Liu; Yonghui Zheng; Zhigang Xie; Yubin Huang; Xiabin Jing
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-11
Journal Detail:
Title:  Journal of controlled release : official journal of the Controlled Release Society     Volume:  -     ISSN:  1873-4995     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8607908     Medline TA:  J Control Release     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
Affiliation:
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China; Graduate School of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
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