The lower-generation polypropylenimine dendrimers are effective gene-transfer agents

Bernd H. Zinselmeyer, Simon P. Mackay, Andreas G. Schatzlein, Ijeoma F. Uchegbu

Research output: Contribution to journalArticle

277 Citations (Scopus)

Abstract

Objective. To evaluate polypropylenimine dendrimers (generations 1-5: DAB 4, DAB 8, DAB 16, DAB 32, and DAB 64) as gene delivery systems. Methods. DNA binding was evaluated by measuring the reduced fluorescence of ethidium bromide, and molecular modelling of dendrimer-DNA complexes also was performed. Cell cytotoxicity was evaluated against the A431 cell line using the MTT assay. In vitro transfection was evaluated against the A431 cell line using the β-galactosidase reporter gene and N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulphate (DOTAP) served as a positive control. Results. Molecular modeling and experimental data revealed that DNA binding increased with dendrimer generation. Cell cytotoxicity was largely generation dependent, and cytotoxicity followed the trend DAB 64 > DAB 32 > DAB 16 > DOTAP > DAB 4 > DAB 8, whereas transfection efficacy followed the trend DAB 8 = DOTAP = DAB 16 > DAB 4 > DAB 32 = DAB 64. Conclusion. The generation 2 polypropylenimine dendrimer combines a sufficient level of DNA binding with a low level of cell cytoxicity to give it optimum in vitro gene transfer activity.

LanguageEnglish
Pages960-967
Number of pages8
JournalPharmaceutical Research
Volume19
Issue number7
DOIs
Publication statusPublished - 31 Jul 2002

Fingerprint

Gene transfer
Dendrimers
Cytotoxicity
Molecular modeling
DNA
Genes
Transfection
Cells
Cell Line
Gene Transfer Techniques
Ethidium
beta-Galactosidase
Reporter Genes
Assays
Fluorescence
poly(propyleneimine)
1,2-dioleoyloxy-3-(trimethylammonium)propane
In Vitro Techniques

Keywords

  • astramol
  • cytotoxicity
  • gene delivery
  • molecular modeling
  • polypropylenimine dendrimers

Cite this

Zinselmeyer, Bernd H. ; Mackay, Simon P. ; Schatzlein, Andreas G. ; Uchegbu, Ijeoma F. / The lower-generation polypropylenimine dendrimers are effective gene-transfer agents. In: Pharmaceutical Research. 2002 ; Vol. 19, No. 7. pp. 960-967.
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The lower-generation polypropylenimine dendrimers are effective gene-transfer agents. / Zinselmeyer, Bernd H.; Mackay, Simon P.; Schatzlein, Andreas G.; Uchegbu, Ijeoma F.

In: Pharmaceutical Research, Vol. 19, No. 7, 31.07.2002, p. 960-967.

Research output: Contribution to journalArticle

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