Linear Poly(ethylenimine) Cross-Linked by Methyl-β-Cyclodextrin for Gene Delivery

Author(s): Wing-Fu Lai, David W. Green and Han-Sung Jung

Volume 14, Issue 4, 2014

Page: [258 - 268] Pages: 11

DOI: 10.2174/1566523214666140612160042

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Poly(ethylenimine) (PEI) is a cationic polymer extensively exploited for non-viral gene delivery; however, its wide application has been impeded by its cytotoxicity. PEI can assume either a branched or linear configuration. Whereas branched PEI (bPEI) is more chemically reactive and can form smaller complexes with DNA under salt-containing conditions, lPEI is generally less toxic and exhibits higher transfection efficiency. In this study, we cross-linked low-molecularweight lPEI with methyl β-cyclodextrin (MβCD) to form MβCD-lPEI (MLP). The structure of MLP was successfully characterized by NMR, FT-IR, MALDI-TOF and elemental analysis. In the standard serum-free transfection environment, MLP could effectively transfect glioblastoma, melanoma and hepatocarcinoma cells. A high transfection efficiency was maintained in the presence of serum. Apart from its high transfection efficiency, MLP was found to have negligible cytotoxicity over a wide range of concentrations and to exhibit a low membrane disruptive capacity ex vivo. MLP warrants further development as a promising gene delivery system for future research.

Keywords: Cancer, cyclodextrin, gene delivery, gene therapy, non-viral gene vector, poly (ethylenimine).

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