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Research Article

Biodistribution and pharmacokinetics of Mad2 siRNA-loaded EGFR-targeted chitosan nanoparticles in cisplatin sensitive and resistant lung cancer models

    Ana Vanessa Nascimento

    CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Gandra, Portugal

    Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Portugal

    Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, MA, USA

    ,
    Florence Gattacceca

    Institut de Recherche en Cancérologie de Montpellier IRCM, INSERM U1194, ICM, Université de Montpellier, Montpellier, France

    ,
    Amit Singh

    Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, MA, USA

    ,
    Hassan Bousbaa

    CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Gandra, Portugal

    Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Universidade do Porto, Portugal

    ,
    Domingos Ferreira

    Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Portugal

    ,
    Bruno Sarmento

    CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Gandra, Portugal

    I3S, Instituto de Investigação e Inovação em Saúde and INEB – Instituto de Engenharia Biomédica, Universidade do Porto, Portugal

    &
    Mansoor M Amiji

    *Author for correspondence:

    E-mail Address: m.amiji@neu.edu

    Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, MA, USA

    Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia

    Published Online:https://doi.org/10.2217/nnm.16.14

    Background: The present study focuses on biodistribution profile and pharmacokinetic parameters of EGFR-targeted chitosan nanoparticles (TG CS nanoparticles) for siRNA/cisplatin combination therapy of lung cancer. Material & methods: Mad2 siRNA was encapsulated in EGFR targeted and nontargeted (NTG) CS nanoparticles by electrostatic interaction. The biodistribution of the nanoparticles was assessed qualitatively and quantitatively in cisplatin (DDP) sensitive and resistant lung cancer xenograft model. Results: TG nanoparticles showed a consistent and preferential tumor targeting ability with rapid clearance from the plasma to infiltrate and sustain within the tumor up to 96 h. They exhibit a sixfold higher tumor targeting efficiency compared with the NTG nanoparticles. Conclusion: TG nanoparticles present as an attractive drug delivery platform for RNAi therapeutics against NSCLC.

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