title: Biodistribution and pharmacokinetics of Mad2 siRNA-loaded EGFR-targeted chitosan nanoparticles in cisplatin sensitive and resistant lung cancer models.
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.
  
  
  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.
  
  
  CONCLUSIONS
  TG nanoparticles present as an attractive drug delivery platform for RNAi therapeutics against NSCLC.
authors.affiliation: 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.
authors.forename: Ana Vanessa
authors.initials: AV
authors.lastname: Nascimento
authors.affiliation: Institut de Recherche en Cancérologie de Montpellier IRCM, INSERM U1194, ICM, Université de Montpellier, Montpellier, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Gattacceca
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, MA, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Singh
authors.affiliation: 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.
authors.forename: Hassan
authors.initials: H
authors.lastname: Bousbaa
authors.affiliation: Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Portugal.
authors.forename: Domingos
authors.initials: D
authors.lastname: Ferreira
authors.affiliation: 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.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sarmento
authors.affiliation: 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.
authors.forename: Mansoor M
authors.initials: MM
authors.lastname: Amiji
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D048271:Chitosan / Q000737:chemistry* / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D064246:Mad2 Proteins / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics / Q000627:therapeutic use; D000067492:RNAi Therapeutics / Q000379:methods; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D064246:Mad2 Proteins; C577698:Mad2l1 protein, mouse; D034741:RNA, Small Interfering; D048271:Chitosan; C541485:EGFR protein, mouse; D066246:ErbB Receptors; D002945:Cisplatin
keywords: EGFR targeting; Mad2 siRNA delivery; biodistribution; chitosan nanoparticles; non-small-cell lung cancer models; pharmacokinetic analysis