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

Nanomedicine (Lond). 2016 Apr;11(7):767-81. doi: 10.2217/nnm.16.14. Epub 2016 Mar 16.

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.

Keywords: EGFR targeting; Mad2 siRNA delivery; biodistribution; chitosan nanoparticles; non-small-cell lung cancer models; pharmacokinetic analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Chitosan / chemistry*
  • Chitosan / metabolism
  • Cisplatin / pharmacology*
  • Cisplatin / therapeutic use
  • Drug Delivery Systems
  • Drug Resistance, Neoplasm
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / therapy*
  • Mad2 Proteins / genetics*
  • Mice
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Nanoparticles / metabolism
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / pharmacokinetics
  • RNA, Small Interfering / therapeutic use
  • RNAi Therapeutics / methods
  • Tissue Distribution

Substances

  • Antineoplastic Agents
  • Mad2 Proteins
  • Mad2l1 protein, mouse
  • RNA, Small Interfering
  • Chitosan
  • EGFR protein, mouse
  • ErbB Receptors
  • Cisplatin