Rapamycin loaded magnetic Fe3O4/carboxymethylchitosan nanoparticles as tumor-targeted drug delivery system: Synthesis and in vitro characterization

Colloids Surf B Biointerfaces. 2015 Apr 1:128:379-388. doi: 10.1016/j.colsurfb.2015.02.035. Epub 2015 Feb 24.

Abstract

A novel tumor-targeted drug delivery system (Fe3O4/CMCS-Rapa NPs) was prepared using magnetic Fe3O4/carboxymethylchitosan nanoparticles (Fe3O4/CMCS NPs) as carrier and rapamycin (Rapa) as the model anti-tumor drug. The morphology, composition, and properties of the Fe3O4/CMCS-Rapa NPs were characterized by Fourier transform infrared spectroscopy (FT-IR), transmission electron microscope (TEM), X-ray diffraction (XRD), thermal analysis (TG/DSC), vibration sample magnetometer (VSM), and drug release kinetics, cytotoxicity, cellular uptake, apoptosis studies in vitro. The results showed that the synthesized Fe3O4/CMCS-Rapa NPs were spherical in shape with an average size of 30±2 nm, the saturated magnetization reached 67.1 emu/g, and the loading efficiency of Rapa was approximately 6.32±0.34%. In addition, the in vitro drug release behavior displayed that the Fe3O4/CMCS NPs exhibited a biphasic drug release pattern with initial burst release and consequently sustained release. Furthermore, the Fe3O4/CMCS-Rapa NPs showed lower cytotoxicity to liver cell line (LO2) and comparatively higher cytotoxicity to human hepatocarcinoma cell line (HepG2) than native Rapa. Fe3O4/CMCS-Rapa NPs could enhance cellular uptake and reduce Rapa drug damage to the normal cells so as to improve the curative effect of drug to tumor cells. All these results demonstrated that the Fe3O4/CMCS-Rapa NPs may be useful as a promising candidate for targeted cancer diagnostic and therapy.

Keywords: Carboxymethylchitosan; Magnetic nanoparticles; Rapamycin; Targeted cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chitosan / analogs & derivatives*
  • Chitosan / chemistry
  • Dose-Response Relationship, Drug
  • Drug Carriers*
  • Drug Compounding
  • Drug Liberation
  • Ferrosoferric Oxide / chemistry*
  • Hepatocytes / drug effects
  • Hepatocytes / pathology
  • Humans
  • Kinetics
  • Magnetite Nanoparticles / chemistry*
  • Magnetite Nanoparticles / ultrastructure
  • Organ Specificity
  • Particle Size
  • Sirolimus / chemistry
  • Sirolimus / pharmacology*

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Magnetite Nanoparticles
  • carboxymethyl-chitosan
  • Chitosan
  • Sirolimus
  • Ferrosoferric Oxide