Glutathione conjugated polyethylenimine on the surface of Fe3O4 magnetic nanoparticles as a theranostic agent for targeted and controlled curcumin delivery

J Biomater Sci Polym Ed. 2018 Jul;29(10):1109-1125. doi: 10.1080/09205063.2018.1427013. Epub 2018 Feb 16.

Abstract

Theranostics with the ability to simultaneous monitoring of treatment progress and controlled delivery of therapeutic agents has become as an emerging therapeutic paradigm in cancer therapy. In this study, we have developed a novel surface functionalized iron oxide nanoparticle using polyethyleneimine and glutathione for targeted curcumin (CUR) delivery and acceptable pH sensitive character. The developed magnetic nanoparticles (MNPs) were physicochemically characterized by FT-IR, XRD, FE-SEM and TEM. The MNPs was obtained in spherical shape with diameter of 50 nm. CUR was efficiently loaded into the MNPs and then in vitro release analyses were evaluated and showed that the prepared MNPs could release higher amount of CUR in acidic medium compared to neutral medium due to the pH sensitive property of the coated polymer. MTT assay confirmed the superior toxicity of CUR loaded MNPs compared to the control nanoparticles. Higher cellular uptake of the MNPs than negative control cells was demonstrated in SK-N-MC cell line. In vitro assessment of MRI properties showed that synthesized MNPs could be used as MRI imaging agent. Furthermore, according to hemolysis assay, the developed formulation exhibited suitable hemocompatibility. In vivo blood circulation analysis of the MNPs also exhibited enhanced serum bioavailability up to 2.5 fold for CUR loaded MNPs compared with free CUR.

Keywords: Curcumin; Glutathione; Iron oxide nanoparticle; Polyethyleneimine, hemocompatibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Biological Transport
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Contrast Media / chemistry
  • Curcumin / pharmacology*
  • Delayed-Action Preparations / chemistry
  • Drug Carriers / chemistry*
  • Drug Carriers / pharmacokinetics
  • Drug Liberation
  • Ferrosoferric Oxide / chemistry*
  • Glutathione / chemistry*
  • Humans
  • Hydrogen-Ion Concentration
  • Magnetic Resonance Imaging
  • Magnetite Nanoparticles / chemistry*
  • Male
  • Molecular Targeted Therapy
  • Particle Size
  • Polyethyleneimine / chemistry*
  • Rats, Wistar
  • Surface Properties
  • Theranostic Nanomedicine

Substances

  • Antineoplastic Agents
  • Contrast Media
  • Delayed-Action Preparations
  • Drug Carriers
  • Magnetite Nanoparticles
  • Polyethyleneimine
  • Glutathione
  • Curcumin
  • Ferrosoferric Oxide