Journal of Pharmaceutical Investigation

, Volume 49, Issue 1, pp 105–114 | Cite as

Charge reduction: an efficient strategy to reduce toxicity and increase the transfection efficiency of high molecular weight polyethylenimine

  • Mehdi Rezaee
  • Leila Gholami
  • Mojtaba Seddighi Gildeh
  • Mohammad RamezaniEmail author
  • Reza Kazemi OskueeEmail author
Original Article


With high potency in treatment of various diseases, gene therapy is mainly hindered by lack of safe and efficient gene delivery vectors. The current study was aimed to develop an efficient non-viral vector with adequate cytotoxicity. To this end, alkylcarboxylate chains (6C, 10C, 16C) were exploited to ameliorate the characteristics of PEI 750 kDa. Briefly, alkylcarboxylate chains with three different lengths (6C, 10C, 16C) were chemically grafted to the primary amine groups of PEI 750 kDa in three percentages (10, 50, and 100%). After evaluating the physicochemical properties of prepared vectors including surface charge, size, buffering capacity, and DNA condensing, their transfection efficiency and cytotoxicity were investigated in Neuro2A cells. The polyplexes size were 158.9–264.5 nm and their zeta potentials were 14–30 mV, while their buffering capacity and DNA condensing were not significantly decreased. The highest transfection efficiency in term of C/P ratio was observed in PEI750-10C-68%, PEI750-10C-7%, and PEI750-6C-7% at C/P ratios of 2, 4, and 6, respectively. Altogether, the decanoylcarboxylate-modified PEI with medium grafting percentages showed promising results as gene delivery vector. To sum up, the modification of high molecular weight PEIs by alkylcarboxylate chains is an efficient approach for development of more efficient non-viral vectors.


Alkylcarboxylate chains Gene delivery Non-viral vectors Polyethylenimine Polyplexes 



This study was supported by Mashhad University of Medical Sciences (MUMS), Mashhad, Iran.

Compliance with ethical standards

Conflict of interest

All authors (M. Rezaee, L. Gholami, M. Seddighi Gildeh, M. Ramezani and R. Kazemi Oskuee) declare that they have no conflict of interest.

Research involving human and animal participants

This article does not contain any studies with human or animal subjects performed by any of the authors.


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Copyright information

© The Korean Society of Pharmaceutical Sciences and Technology 2018

Authors and Affiliations

  • Mehdi Rezaee
    • 1
    • 2
  • Leila Gholami
    • 3
  • Mojtaba Seddighi Gildeh
    • 4
  • Mohammad Ramezani
    • 4
    Email author
  • Reza Kazemi Oskuee
    • 1
    • 5
    Email author
  1. 1.Department of Medical Biotechnology, Faculty of MedicineMashhad University of Medical SciencesMashhadIran
  2. 2.Student Research CommitteeMashhad University of Medical SciencesMashhadIran
  3. 3.Department of Modern Sciences and Technologies, Faculty of MedicineMashhad University of Medical SciencesMashhadIran
  4. 4.Pharmaceutical Research CenterPharmaceutical Technology Institute, Mashhad University of Medical SciencesMashhadIran
  5. 5.Nanotechnology Research CenterMashhad University of Medical SciencesMashhadIran

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