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The Effects of PVP(Fe(III)) Catalyst on Polymer Molecular Weight and Gene Delivery via Biodegradable Cross-Linked Polyethylenimine
Shum, Victor W. T. Gabrielson, Nathan P. Forrest, M. Laird Pack, Daniel W.
Shum, Victor W. T.
Gabrielson, Nathan P.
Forrest, M. Laird
Pack, Daniel W.
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Abstract
Purpose
Crosslinked, degradable derivatives of low-molecular-weight polyethylenimine (PEI) are relatively efficient and non-cytotoxic gene delivery agents. To further investigate these promising materials, a new synthetic approach was developed using a poly(4-vinylpyridine)-supported Fe(III) catalyst (PVP(Fe(III))) that provides more facile synthesis and enhanced control of polymer molecular weight.
Methods
Biodegradable polymers (D.PEI) comprising 800-Da PEI crosslinked with 1,6-hexanediol diacrylate and exhibiting molecular weights of 1.2, 6.2, and 48 kDa were synthesized utilizing the PVP(Fe(III)) catalyst. D.PEI/DNA polyplexes were characterized using gel retardation, ethidium bromide exclusion, heparan sulfate displacement, and dynamic light scattering. In vitro transfection, cellular uptake, and cytotoxicity of the polyplexes were tested in human cervical cancer cells (HeLa) and human breast cancer cells (MDA-MB-231).
Results
D.PEIs tightly complexed plasmid DNA and formed 320- to 440-nm diameter polyplexes, similar to those comprising non-degradable, 25-kDa, branched PEI. D.PEI polyplexes mediated 2- to 5-fold increased gene delivery efficacy compared to 25-kDa PEI and exhibited 20% lower cytotoxicity in HeLa and no toxicity in MDA-MB-231. In addition, 2- to 7-fold improved cellular uptake of DNA was achieved with D.PEI polyplexes.
Conclusions
PVP(Fe(III)) catalyst provided a more controlled synthesis of D.PEIs, and these materials demonstrated improved in vitro transfection efficacy and reduced cytotoxicity.
Description
The original publication is available at www.springerlink.com
Date
2011-09-03
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Publisher
American Association of Pharmaceutical Scientists
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Keywords
Polyethylenimine, Non-viral gene delivery, Biodegradable polymer, Polymer supported ferric chloride
Citation
Shum, Victor W.T. et al. “The Effects of PVP(Fe(III)) Catalyst on Polymer Molecular Weight and Gene Delivery via Biodegradable Cross-Linked Polyethylenimine.” Pharmaceutical research 29.2 (2012): 500–510.