Document Detail


Chitosan N-betainates/DNA self-assembly nanoparticles for gene delivery: in vitro uptake and transfection efficiency.
MedLine Citation:
PMID:  19135139     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aim of this work is to investigate the effect of betaine substitution degree of chitosan N-betainates (CsB) on cellular uptake, cytotoxicity and transfection efficiency of CsB/DNA complex nanoparticles (CsBNs) against COS-7 and MDA-MB-468 cells. The polymers with three substitution degrees (CsB12, CsB47 and CsB85) complexed with pDNA formed CsBN12s, CsBN47s and CsBN85s. The CsBNs showed less pH dependency with smaller particle size and higher zeta potential than that of chitosan/pDNA complex nanoparticles (CsNs) at neutral pH. CsBN85s showed stronger cellular uptake than that of CsBN47s or CsBN12s. CsBNs showed higher cytotoxicity than CsNs, and a trend increasing toxicity with substitution degree increasing. In COS-7 cells, the transfection efficiency increased with the substitution degree increasing, while the opposite result was observed in MDA-MB-468 cells. Chitosan modified with betaine could increase its ability to facilitate DNA uptake and its cytotoxicity, both of which showed the influence on transfection efficiency. It was able to increase cellular uptake and transfection efficiency of complex nanoparticles in COS-7 cells to increase betaine substitution of CsB, however, the higher sensitivity of MDA-MB-468 cells to CsBs led to decreased transfection efficiency due to the increased cytotoxicity with betaine substitution increasing. The predominant role of cellular uptake or toxicity in affecting transfection efficiency was different in two cell lines. These results provided an important guidepost for further development of chitosan derivatives/pDNA complexes as non-viral gene vectors.
Authors:
Yu Gao; Zhiwen Zhang; Lingli Chen; Wangwen Gu; Yaping Li
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-12-24
Journal Detail:
Title:  International journal of pharmaceutics     Volume:  371     ISSN:  1873-3476     ISO Abbreviation:  Int J Pharm     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-30     Completed Date:  2009-08-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7804127     Medline TA:  Int J Pharm     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  156-62     Citation Subset:  IM    
Affiliation:
Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Betaine / analogs & derivatives*,  chemistry,  toxicity
COS Cells
Cell Line, Tumor
Cell Survival
Cercopithecus aethiops
Chitosan / analogs & derivatives*,  chemistry,  toxicity
DNA / administration & dosage*,  genetics
Gene Transfer Techniques*
Humans
Hydrogen-Ion Concentration
Nanoparticles / chemistry*,  toxicity
Physicochemical Phenomena
Transfection
Chemical
Reg. No./Substance:
107-43-7/Betaine; 9007-49-2/DNA; 9012-76-4/Chitosan

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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