Linear Poly(ethylenimine) Cross-Linked by Methyl-β-Cyclodextrin for Gene Delivery
David W. Green,
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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