Physicochemical and Biological Evaluation of siRNA Polyplexes Based on PEGylated Poly(amido amine)s

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Vader, P. and Aa, L.J. van der and Engbersen, J.F.J. and Storm, G. and Schiffelers, R.M. (2012) Physicochemical and Biological Evaluation of siRNA Polyplexes Based on PEGylated Poly(amido amine)s. Pharmaceutical research, 29 (2). 352 - 361. ISSN 0724-8741

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Abstract:Purpose
Use of RNA interference as novel therapeutic strategy is hampered by inefficient delivery of its mediator, siRNA, to target cells. Cationic polymers have been thoroughly investigated for this purpose but often display unfavorable characteristics for systemic administration, such as interactions with serum and/or toxicity.
Methods
We report the synthesis of a new PEGylated polymer based on biodegradable poly(amido amine)s with disulfide linkages in the backbone. Various amounts of PEGylated polymers were mixed with their unPEGylated counterparts prior to polyplex formation to alter PEG content in the final complex.
Results
PEGylation effectively decreased polyplex surface charge, salt- or serum-induced aggregation and interaction with erythrocytes. Increasing amount of PEG in formulation also reduced its stability against heparin displacement, cellular uptake and subsequent silencing efficiency. Yet, for polyplexes with high PEG content, significant gene silencing efficacy was found, which was combined with almost no toxicity.
Item Type:Article
Copyright:© 2012 The Author(s)
Faculty:
Science and Technology (TNW)
Research Group:
Link to this item:http://purl.utwente.nl/publications/81739
Official URL:http://dx.doi.org/10.1007/s11095-011-0545-z
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