期刊
JOURNAL OF CONTROLLED RELEASE
卷 153, 期 3, 页码 262-268出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2011.04.017
关键词
Polyplexes, self-assembled architecture; Buffer capacity; Complexes formation constants; Stability; Size and zeta-potential; siRNA transfection
资金
- European Commission [NMP4-CT-2006-026668]
A library of mono-methoxyl-poly(ethylene glycol)-block-poly(epsilon-caprolactone) (mPEG-PCL) modified hyperbranched PEI copolymers (hy-PEI-PCL-mPEG) was synthesized to establish structure function relationships for siRNA delivery. These amphiphilic block-copolymers were thought to provide improved colloidal stability and endosomal escape of polyplexes containing siRNA. The influence of the mPEG chain length, PCL segment length, hy-PEI molecular weight and the graft density on their biophysical properties was investigated. In particular, buffer capacity, complex formation constants, gene condensation, polyplex stability, polyplex size and zeta-potential were measured. It was found that longer mPEG chains, longer PCL segments and higher graft density beneficially affected the stability and formation of polyplexes and reduced the zeta-potential of siRNA polyplexes. Significant siRNA mediated knockdown was observed for hy-PEI25k-(PCL900-mPEG2k)(1) at N/P 20 and 30, implying that the PCL hydrophobic segment played a very important role in siRNA transfection. These gene delivery systems merit further investigation under in vivo conditions. (C) 2011 Elsevier B.V. All rights reserved.
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