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Comparison of the effectiveness of polyethylenimine, polyamidoamine and chitosan in transferring plasmid encoding interleukin-12 gene into hepatocytes

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Abstract

Interleukin-12 (IL-12) has been proposed for cancer immunotherapy due to its versatile antitumor and antiangiogenesis effects. Although cancer immunotherapy through systemic administration of IL-12 has shown antitumor effects in tumor-bearing mice, broad application of recombinant IL-12 protein has been limited by its cytotoxicity. Therefore, the use of various polycationic polymers such as polyethylenimine (PEI), polyamidoamine (PAMAM) and chitosan has been considered as an effective strategy to transfer plasmid encoding IL-12 gene into cells. In this investigation, polyplexes (polymer/pDNA complexes) were prepared using PEI, PAMAM and chitosan at different N/P ratios and their ability in transferring plasmid encoding IL-12 gene was evaluated. Furthermore, these polyplexes were characterized and compared with regarding their cytotoxicity, DNA condensation ability, particle size, zeta potential, buffering capacity and pDNA protection against enzyme degradation. The results revealed that the polyplexes formulated with 25 kDa PEI and chitosan had the highest transfection efficiencies. The highest level of IL-12 gene expression was achieved by the nanoparticles prepared by 25 kDa PEI where they could increase the level of gene expression up to 12 times compared to that of naked plasmid encoding IL-12 gene. These results suggest that 25 kDa PEI and chitosan are the best candidates for adding targeting ligands into their structures in order to create a liver targeting gene delivery system.

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Authors and Affiliations

  1. Department of Pharmaceutical Biotechnology and Pharmaceutical Sciences Research Center, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Ali Dehshahri, Samira Hossaini Alhashemi, Zahra Sabahi, Erfaneh Mohazabieh & Mahin Fadaei

  2. Department of Pharmacology & Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Akram Jamshidzadeh

  3. Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Soliman Mohammadi Samani

  4. Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Hossein Sadeghpour

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  1. Ali Dehshahri
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  2. Samira Hossaini Alhashemi
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Correspondence to Ali Dehshahri.

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Dehshahri, A., Alhashemi, S.H., Jamshidzadeh, A. et al. Comparison of the effectiveness of polyethylenimine, polyamidoamine and chitosan in transferring plasmid encoding interleukin-12 gene into hepatocytes. Macromol. Res. 21, 1322–1330 (2013). https://doi.org/10.1007/s13233-013-1180-9

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  • DOI: https://doi.org/10.1007/s13233-013-1180-9

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