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

Author:

Nascimento Ana Vanessa123,Gattacceca Florence4,Singh Amit3,Bousbaa Hassan15,Ferreira Domingos2,Sarmento Bruno16,Amiji Mansoor M37

Affiliation:

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

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

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

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

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

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

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

Abstract

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.

Publisher

Future Medicine Ltd

Subject

Development,General Materials Science,Biomedical Engineering,Medicine (miscellaneous),Bioengineering

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