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Development of a Low Toxicity, Effective pDNA Vector Based on Noncovalent Assembly of Bioresponsive Amino-β-cyclodextrin:Adamantane-Poly(vinyl alcohol)-Poly(ethylene glycol) Transfection Complexes.
MedLine Citation:
PMID:  22551467     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
A host:guest-derived gene delivery vector has been developed, based on the self-assembly of cationic β-CD derivatives with a poly(vinyl alcohol) (MW 27 kDa) (PVA) main chain polymer bearing poly(ethylene glycol) (MW 750) (PEG) or MW 2000 PEG and acid-labile adamantane-modified (Ad) grafts through an acid-sensitive benzylidene acetal linkage. These components were investigated for their ability to promote supramolecular complex formation with pDNA using two different assembly schemes, involving either precomplexation of the pendent Ad-PVA-PEG polymer with the cationic β-CD derivatives before pDNA condensation (method A) or pDNA condensation with the cationic β-CD derivatives prior to addition of Ad-PVA-PEG to engage host:guest complexation (method B). The pendent polymers were observed to degrade under acidic conditions while remaining intact for more than 5 days at pH 7. HeLa cell culture data show that these materials have 10(3)-fold lower cytotoxicities than 25 kDa bPEI while maintaining transfection efficiencies that are superior to those observed for this benchmark cationic polymer transfection reagent when the method A assembly scheme is employed. These findings suggest that degradable cationic polymer constructs employing multivalent host:guest interactions may be an effective and low-toxicity vehicle for delivering nucleic acid cargo to target cells.
Authors:
Aditya Kulkarni; Wei Deng; Seok-Hee Hyun; David H Thompson
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-2
Journal Detail:
Title:  Bioconjugate chemistry     Volume:  -     ISSN:  1520-4812     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9010319     Medline TA:  Bioconjug Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Departments of Chemistry and Biomedical Engineering, Purdue University , 560 Oval Drive, West Lafayette, Indiana 47907, United States.
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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