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Evaluation of Efficiency of Modified Polypropylenimine (PPI) with Alkyl Chains as Non-viral Vectors Used in Co-delivery of Doxorubicin and TRAIL Plasmid

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Abstract

In this study, co-delivery system was achieved via plasmid encoding TNF related apoptosis inducing ligand (pTRAIL) and doxorubicin (DOX) using carrier based on polypropylenimine (PPI) modified with 10-bromodecanoic acid. Incorporation of alkylcarboxylate chain to PPIs (G4 and G5) could improve transfection efficiency via overcoming the plasma membrane barrier of the cells and decrease cytotoxicity of PPI. Characterization of fabricated NPs revealed that PPI G5 in which 30% of primary amines were substituted by alkyl carboxylate chain (PPI G5-Alkyl 30%) has higher drug loading as compared to the other formulations. PPI G5-Alkyl 30% indicated a decreased drug release may be due to alkyl chains on the surface of PPI, which serve as an additional hindrance for drug diffusion. In vitro cytotoxicity experiments demonstrated that co-delivery system induced apoptosis of tumor cells more efficiently than each of delivery system alone. Furthermore, these results revealed that our combined delivery platform of pTRAIL and DOX using Alkyl-modified PPI G5 can significantly improve the anti-tumor activity and this strategy might develop a new therapeutic window for cancer treatment.

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Author notes

  1. Mahboubeh Ebrahimian and Sahar Taghavi contributed equally to this work.

Authors and Affiliations

  1. Division of Biotechnology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran

    Mahboubeh Ebrahimian

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

    Mahboubeh Ebrahimian, Sahar Taghavi, Sara Amel Farzad & Mohammad Ramezani

  3. School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Maryam Ghoreishi & Shahrzad Sedghi

  4. Nanotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Maryam Hashemi

Authors
  1. Mahboubeh Ebrahimian
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  2. Sahar Taghavi
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  3. Maryam Ghoreishi
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  4. Shahrzad Sedghi
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  5. Sara Amel Farzad
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  6. Mohammad Ramezani
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  7. Maryam Hashemi
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Correspondence to Maryam Hashemi.

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Ebrahimian, M., Taghavi, S., Ghoreishi, M. et al. Evaluation of Efficiency of Modified Polypropylenimine (PPI) with Alkyl Chains as Non-viral Vectors Used in Co-delivery of Doxorubicin and TRAIL Plasmid. AAPS PharmSciTech 19, 1029–1036 (2018). https://doi.org/10.1208/s12249-017-0913-z

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  • DOI: https://doi.org/10.1208/s12249-017-0913-z

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