Optimization of poly(amido amine)s as vectors for siRNA delivery

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Aa, L.J. van der and Vader, P. and Storm, G and Schiffelers, R.M. and Engbersen, J.F.J. (2011) Optimization of poly(amido amine)s as vectors for siRNA delivery. Journal of Controlled Release, 150 (2). pp. 177-186. ISSN 0168-3659

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Abstract:By Michael addition polymerization of N,N'-cystaminebisacrylamide (CBA) with variable ratios of 4-amino-1-butanol (ABOL) and ethylene diamine (EDA) or triethylenetetramine (TETA), poly(amido amine) copolymers could be obtained with tunable charge densities. The copolymers were optimized to serve as nonviral vectors in RNA interference (RNAi) to form stable, nanosized polyplexes with siRNA with maximum transfection efficacy. It was observed that at least 20–30% EDA or TETA amino units in the copolymers is necessary to encapsulate siRNA into small and stable polyplexes (< 200 nm). Incorporation of higher amounts of EDA or TETA in the copolymers did not further improve polyplex formation and stability, but the increased cationic charge in these copolymers resulted in increased cytotoxicity and hemolytic activity. Copolymers with 20% EDA showed excellent gene silencing properties in vitro (70% luciferase knockdown in H1299 cells) with negligible cytotoxicity
Item Type:Article
Copyright:© 2011, Elsevier
Faculty:
Science and Technology (TNW)
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Link to this item:http://purl.utwente.nl/publications/77518
Official URL:http://dx.doi.org/10.1016/j.jconrel.2010.11.030
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