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  • Title: A biodegradable low molecular weight polyethylenimine derivative as low toxicity and efficient gene vector.
    Author: Wen Y, Pan S, Luo X, Zhang X, Zhang W, Feng M.
    Journal: Bioconjug Chem; 2009 Feb; 20(2):322-32. PubMed ID: 19152330.
    Abstract:
    Polyethylenimine (PEI) is a class of cationic polymers proven to be effective for gene delivery. However, PEI is nondegradable and the molecular weight of PEI affects the cytotoxicity and gene transfer activity. Aiming to prepare a biodegradable gene vector with high transfection efficiency and low cytotoxicity, we conjugated low molecular weight (LMW) PEIs to the biodegradable backbone polyglutamic acids derivative (PEG-b-PBLG) by aminolysis to form PEIs combined PEG-b-PLG-g-PEIs (GGI). Two copolymers, GGI 30 and GGI 40, were synthesized. The chemistry of GGI was characterized using IR, 1H NMR and 13C NMR, GPC, and CD, respectively. The degradation behaviors of copolymer GGI in papain solution were investigated. GGIs showed good DNA condensation ability and high protection of DNA from nuclease degradation. The zeta potential of the GGI/pDNA polyplexes was approximately 15 mV, and the particle size was in the range 102-138 nm at N/P ratios between 10 and 30. The particle size and the morphology of the polyplex was further confirmed by transmission electron microscope (TEM). In cytotoxicity assay, GGIs were significantly less toxic than PEI 25k. The degradation product of GGI exhibited negligible effects on cells even at high copolymer concentration. The results of GFP flow cytometry and fluorescence imaging showed that the trasnfection efficiencies of GGIs were all markedly higher than PEI 25k in Hela, HepG2, Bel 7402, and 293 cell lines. Importantly, the presence of serum had a lower inhibitive effect on the transfection activity of GGI in comparison to PEI 25k and Lipofectamine 2000. Therefore, PEG-b-PLG-g-PEI copolymers may be attractive cationic polymers for nonviral gene therapy.
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