A novel non-viral vector for DNA delivery based on low molecular weight, branched polyethylenimine: effect of molecular weight on transfection efficiency and cytotoxicity

Pharm Res. 1999 Aug;16(8):1273-9. doi: 10.1023/a:1014861900478.


Purpose: Low molecular weight branched polyethylenimine (LMW-PEI) was synthesized and studied as a DNA carrier for gene delivery with regard to physico-chemical properties, cytotoxicity, and transfection efficiency.

Methods: The architecture of LMW-PEI, synthesized by acid catalyzed ring-opening polymerization of aziridine was characterized by size exclusion chromatography in combination with laser light scattering and 13C-NMR-spectroscopy. In vitro cytotoxic effects were quantified by LDH and MTT assay and visualized by transmission electron microscopy. The potential for transgene expression was monitored in ECV304 cells using luciferase driven by a SV40 promotor as reporter gene system.

Results: LMW-PEI (Mw 11'900 D) with a low degree of branching was synthesized as a DNA carrier for gene delivery. In contrast to high molecular weight polyethylenimines (HMW-PEI; Mw 1'616'000 D), the polymer described here showed a different degree of branching and was less cytotoxic in a broad range of concentrations. As demonstrated by transmission electron microscopy the LMW-PEI formed only small aggregates which were efficiently taken up by different cells in the presence of serum, most likely by an endocytic pathway. LMW-PEI yielded transfection efficiencies measured via expression of the reporter gene luciferase which were up to two orders of magnitude higher than those obtained with HMW-PEI. The reporter gene expression was concentration dependent, but in contrast to lipofection independent of serum addition.

Conclusions: The LMW-PEI described here is a new, highly efficient, and non-cytotoxic vector with a favorable efficiency/toxicity profile for gene therapeutic applications.

MeSH terms

  • Animals
  • Cells, Cultured
  • DNA / administration & dosage*
  • Drug Carriers
  • Electrophoresis, Agar Gel
  • Fibroblasts / drug effects
  • Gene Transfer Techniques
  • Genetic Vectors*
  • Mice
  • Molecular Weight
  • Polyethyleneimine / chemistry
  • Polyethyleneimine / pharmacology*
  • Polyethyleneimine / toxicity
  • Transfection / methods*


  • Drug Carriers
  • Polyethyleneimine
  • DNA