Effective delivery of hydrophobic drugs to breast and liver cancer cells using a hybrid inorganic nanocarrier: A detailed investigation using cytotoxicity assays, fluorescence imaging and flow cytometry

Eur J Pharm Biopharm. 2018 Jul:128:18-26. doi: 10.1016/j.ejpb.2018.04.001. Epub 2018 Apr 3.

Abstract

This study was focused on developing a drug carrier system composed of a polymer containing hydroxyapatite (HAp) shell and a magnetic core of iron oxide nanoparticles. Doxorubicin and/or curcumin were loaded into the carrier via a simple diffusion deposition approach, with encapsulation efficiencies (EE) for curcumin and doxorubicin of 93.03 ± 0.3% and 97.37 ± 0.12% respectively. The co-loading of curcumin and doxorubicin led to a total EE of 76.02 ± 0.48%. Release studies were carried out at pH 7.4 and 5.3, and revealed a greater extent of release at pH 5.3, showing the formulations to have potential applications in tumor microenvironments. Cytotoxicity assays, fluorescence imaging and flow cytometry demonstrated that the formulations could effectively inhibit the growth of MCF-7 (breast) and HEpG2 (liver) cancer cells, being more potent than the free drug molecules both in terms of dose and duration of action. Additionally, hemolysis tests and cytotoxicity evaluations determined the drug-loaded carriers to be non-toxic towards non-cancerous cells. These formulations thus have great potential in the development of new cancer therapeutics.

Keywords: Curcumin; Doxorubicin; HEpG2; Hydroxyapatite; Iron oxide; MCF7.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Breast Neoplasms / drug therapy*
  • Cell Proliferation / drug effects
  • Curcumin / administration & dosage
  • Doxorubicin / administration & dosage
  • Drug Carriers / chemistry*
  • Durapatite / chemistry
  • Female
  • Ferric Compounds / chemistry
  • Flow Cytometry
  • Hemolysis / drug effects
  • Hep G2 Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Hydrophobic and Hydrophilic Interactions
  • Liver Neoplasms / drug therapy*
  • MCF-7 Cells
  • Male
  • Nanoparticles / chemistry
  • Optical Imaging
  • Polymers / chemistry
  • Rats, Wistar

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Ferric Compounds
  • Polymers
  • ferric oxide
  • Doxorubicin
  • Durapatite
  • Curcumin