In vitro biologic efficacy of sunitinib drug-eluting beads on human colorectal and hepatocellular carcinoma-A pilot study

PLoS One. 2017 Apr 6;12(4):e0174539. doi: 10.1371/journal.pone.0174539. eCollection 2017.

Abstract

Purpose: Sunitinib drug eluting beads (DEB) are a novel anti-angiogenic bead preparation for use in transarterial chemoembolization. However, systematic studies of sunitinib DEB's effect on cancer cells have not been reported. Herein, we assess their direct biologic efficacy against carcinoma cell lines and correlate cell viability with drug release in vitro.

Materials and methods: Sunitinib-HCl (10mg/mL) in Milli-Q water was mixed with LC Bead® 300-500μm (Biocompatibles UK Ltd.). Loading and release were assessed by measurement of drug UV absorbance using UV-visible spectrophotometer. Viability of human colorectal cancer (CRC, HCT116 and HT29) and hepatocellular carcinoma (HCC, HepG2) cells upon exposure to sunitinib DEB was measured using a bioluminescent assay. Drug concentration during exposure was quantified using HPLC.

Results: When added to cultured HepG2 cells, sunitinib DEB rapidly inhibited viability with a significant decrease observed within 1 hour of incubation. Viability of HCT116 and HT29 cells decreased relatively slower, with significant reductions observed after 8 and 24 hours, respectively. After 24 hours there was nearly complete inhibition of all three cell lines. There was no difference in viability observed between cells treated with 5 μl, 10 μL, or 20 μL of sunitinib DEB. HPLC analysis of the cell culture supernatant demonstrated saturation of the cell medium within approximately 4 hours for each amount added, with sunitinib achieving a final concentration of 17.61 μM (SE ±1.01).

Conclusions: Sunitinib can be efficiently loaded to and released from LC beads, and the resulting sunitinib DEB demonstrate strong in vitro inhibition of human CRC and HCC cells.

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Colorectal Neoplasms / pathology*
  • Drug-Eluting Stents*
  • Humans
  • In Vitro Techniques
  • Indoles / administration & dosage*
  • Indoles / pharmacokinetics
  • Liver Neoplasms / pathology*
  • Pyrroles / administration & dosage*
  • Pyrroles / pharmacokinetics
  • Sunitinib

Substances

  • Antineoplastic Agents
  • Indoles
  • Pyrroles
  • Sunitinib

Grants and funding

The authors received no specific funding for this work.