Natural polymer functionalized graphene oxide for co-delivery of anticancer drugs: In-vitro and in-vivo

Int J Biol Macromol. 2018 Jul 1:113:515-525. doi: 10.1016/j.ijbiomac.2018.02.153. Epub 2018 Feb 27.

Abstract

The present study focuses on the development of a chitosan functionalized nanobiocomposite for the co-delivery of two anti-cancer drugs camptothecin (CPT) and 3,3'‑Diindolylmethane (DIM). The difference in the mechanism of action of the two drugs makes them a promising candidate to produce a synergistic effect against breast cancer. Herein a nanobiocomposite was developed by functionalizing a natural polymer chitosan to graphene oxide nanoparticles and decorated with folic acid. The nanobiocomposite thus synthesized was loaded with camptothecin and 3,3'‑Diindolylmethane and characterized by X-ray diffractometer (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), UV-visible spectroscopy (UV) and atomic force microscopy (AFM).Biocompatibility was assayed by hemolysis and anti-inflammatory assay. The cellular toxicity was measured by 3‑(4,5‑Dimethylthiazol‑2‑yl)‑2,5‑Diphenyltetrazolium Bromide (MTT), Sulforhodamine B (SRB) and cell death assay against MCF-7 cell lines. Further in vivo studies were carried out to analyze the biodistribution of the drug, blood biochemical analysis and bioavailability of the drug. The data revealed a significant increase in anticancer activity after co-loading of CPT and DIM to the nanocarrier. Also in-vivo studies revealed that DIM successfully masked the toxic effects produced by CPT.

Keywords: 3,3′‑Diindolylmethane; Bioavailability; Biodistribution; Camptothecin; Cancer; Chitosan; Graphene oxide; Nanobiocomposite.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacokinetics
  • Anti-Inflammatory Agents / pharmacology
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology
  • Biological Availability
  • Camptothecin / chemistry
  • Camptothecin / pharmacokinetics
  • Camptothecin / pharmacology
  • Cell Death / drug effects
  • Drug Carriers / chemistry*
  • Drug Synergism
  • Female
  • Graphite / chemistry*
  • Hemolysis / drug effects
  • Humans
  • Indoles / chemistry
  • Indoles / pharmacokinetics
  • Indoles / pharmacology
  • MCF-7 Cells
  • Nanocomposites / chemistry
  • Oxides / chemistry*
  • Polymers / chemistry*
  • Rats
  • Rats, Wistar
  • Tissue Distribution

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Drug Carriers
  • Indoles
  • Oxides
  • Polymers
  • Graphite
  • 3,3'-diindolylmethane
  • Camptothecin