Superparamagnetic chitosan nanocomplexes for colorectal tumor-targeted delivery of irinotecan

Int J Pharm. 2020 Jun 30:584:119394. doi: 10.1016/j.ijpharm.2020.119394. Epub 2020 May 11.

Abstract

Conventional chemotherapy is effective for metastatic tumors widely present in colorectal cancer patients; however, chemotherapy may cause severe systemic toxicity due to a lack of specificity towards cancer cells. Effective delivery systems that can enhance targeted drug delivery to the desired tumor site and simultaneously protect the activity of drugs are in high demand. To that end, this study developed chitosan-based polyelectrolyte complexes (PECs) with the orientation of superparamagnetic nanoparticles, which enables the targeting delivery of the first-line model drug irinotecan (IRT) to the tumor area under a magnetic field. Colloidal PECs were mildly and facilely fabricated with chitosan and poly(glutamic acid) (PGA) via an all-in-water process, excluding the use of any potentially toxic chemicals. Iso-dispersed superparamagnetic Fe3O4 nanoparticles with relatively small particle diameters (~10 nm) were embedded into the IRT-loaded nano-PECs. The optimized nano-PECs showed high drug encapsulation capacity and improved anti-colon cancer cell efficacy compared with the free drug. Furthermore, the magnetic nano-PECs exhibited effective internalization by colon tumor cells, and favorable tumor-targeting ability was demonstrated via in vivo biodistribution study. Therefore, this magnetic targeted drug delivery nano-PECs system provides a promising platform to overcome the side effects of conventional chemotherapy for colorectal cancer.

Keywords: Colon cancer; Drug delivery; Irinotecan; Nanocomplexes; Nanomedicine; Superparamagnetic iron oxide.

MeSH terms

  • Animals
  • Cell Survival
  • Chemistry, Pharmaceutical / methods*
  • Chitosan / chemistry*
  • Colorectal Neoplasms / drug therapy
  • Drug Carriers / chemistry
  • Drug Liberation
  • Drug Stability
  • Female
  • HCT116 Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Irinotecan / administration & dosage
  • Irinotecan / pharmacokinetics
  • Irinotecan / pharmacology*
  • Magnetic Iron Oxide Nanoparticles / chemistry*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Particle Size
  • Polyelectrolytes / chemistry
  • Polyglutamic Acid / chemistry
  • Surface Properties
  • Tissue Distribution
  • Topoisomerase I Inhibitors / administration & dosage
  • Topoisomerase I Inhibitors / pharmacokinetics
  • Topoisomerase I Inhibitors / pharmacology*

Substances

  • Drug Carriers
  • Polyelectrolytes
  • Topoisomerase I Inhibitors
  • Polyglutamic Acid
  • Irinotecan
  • Chitosan