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Preparation of Effective and Safe Gene Carriers by Grafting Alkyl Chains to Generation 5 Polypropyleneimine

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Abstract

Gene therapy is a novel method to treat a variety of diseases including genetic disorders and cancer. Nonviral gene carriers have now gained considerable attention as gene carrier systems. Polyamidoamine (PAMAM) and polypropyleneimine (PPI) are the two most widely used denderimers in gene delivery studies. The aim of the current study was to investigate the effects of modification of generation 5 polypropyleneimine (G5 PPI) dendrimers with alkanoate groups as hydrophobic moieties on DNA transfection and cytotoxicity. Six, 10, and 16 carbon derivatives of bromoalkanoic acids were conjugated onto PPI with 10%, 30%, and 50% of surface amine grafting. Ethidium bromide exclusion assay results proved the ability of modified carriers to condense DNA. Transfection assay showed higher DNA delivery potential for 30% and 50% grafting with decanoate moieties compared to native G5 PPI and SuperfectTM. 3-(4,5-Dimethylthiazol-2-yl)-2,5-di phenyltetrazolium bromide (MTT) and apoptosis experiments showed lower toxicity for modified carriers compared to unmodified PPI. The hemolytic effect of grafted carriers was not significantly different from G5 PPI. Size and zeta potential measurements revealed that polyplex size was less than 200 nm and electrical charges were in the range 14–25 mV. The hydrophobic modifications improved transfection activity and toxicity of G5 PPI without negatively affecting hemocompatibility. These modified carriers are therefore promising candidates for further in vivo investigations.

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Authors and Affiliations

  1. Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Maryam Hashemi

  2. Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Hamideh Parhiz, Ahad Mokhtarzadeh, Sara Amel Farzad & Mohammad Ramezani

  3. Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Hamideh Parhiz, Seyed Meghdad Tabatabai & Haniyeh Rezagholizadeh Shirvan

  4. School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran

    Ahad Mokhtarzadeh

Authors
  1. Maryam Hashemi
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  2. Hamideh Parhiz
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  3. Ahad Mokhtarzadeh
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  4. Seyed Meghdad Tabatabai
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  5. Sara Amel Farzad
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  6. Haniyeh Rezagholizadeh Shirvan
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  7. Mohammad Ramezani
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Corresponding author

Correspondence to Mohammad Ramezani.

Additional information

Ahad Mokhtarzadeh and Seyed Meghdad Tabatabai contributed equally to this work.

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Hashemi, M., Parhiz, H., Mokhtarzadeh, A. et al. Preparation of Effective and Safe Gene Carriers by Grafting Alkyl Chains to Generation 5 Polypropyleneimine. AAPS PharmSciTech 16, 1002–1012 (2015). https://doi.org/10.1208/s12249-015-0284-2

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  • DOI: https://doi.org/10.1208/s12249-015-0284-2

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