Polyelectrolyte Carboxymethyl Cellulose for Enhanced Delivery of Doxorubicin in MCF7 Breast Cancer Cells: Toxicological Evaluations in Mice Model

Pharm Res. 2019 Mar 18;36(5):68. doi: 10.1007/s11095-019-2598-3.

Abstract

Purpose: Chemotherapy as an important tool for cancer treatment faces many obstacles such as multidrug resistance and adverse toxic effects on healthy tissues. Drug delivery systems have opened a new window to overcome these problems.

Methods: A polyelectrolyte carboxymethyl cellulose polymer as a magnetic nanocarrier was synthesized for enhancing delivery and uptake of doxorubicin in MCF7 breast cancer cells and decreasing the adverse toxic effects to healthy tissues.

Results: The physicochemical properties of developed nanocarrier showed that it can be used in drug delivery purposes. The efficiency of the delivery system was assessed by loading and release studies. Besides, biological assays including protein-particle interaction, hemolysis assay, cytotoxicity study, cellular uptake, and apoptosis analysis were performed. All results persuaded us to investigate the cytotoxic effects of nanocarrier in an animal model by determining the biochemical parameters attributed to organ injuries, and hematoxylin and eosin (H&E) staining for histopathological manifestations. We observed that the nanocarrier has no toxic effect on healthy tissues, while, it is capable of reducing the toxic side effects of doxorubicin by more cellular internalization.

Conclusion: Chemical characterizations and biological studies confirmed that developed nanocarrier with permanent cationic groups of imidazolium and anionic carboxylic acid groups is an effective candidate for anticancer drug delivery.

Keywords: doxorubicin toxicity MCF7 breast cancer cells; enhanced drug delivery; polyelectrolyte carboxymethyl cellulose.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / toxicity
  • Apoptosis / drug effects
  • Carboxymethylcellulose Sodium / chemistry*
  • Carboxymethylcellulose Sodium / toxicity
  • Cell Membrane Permeability
  • Cell Survival / drug effects
  • Doxorubicin / administration & dosage*
  • Doxorubicin / toxicity
  • Drug Carriers / chemistry*
  • Drug Carriers / toxicity
  • Drug Liberation
  • Humans
  • MCF-7 Cells
  • Magnetite Nanoparticles / chemistry
  • Male
  • Mice
  • Particle Size
  • Polyelectrolytes / chemistry*
  • Polyelectrolytes / toxicity
  • Surface Properties

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Magnetite Nanoparticles
  • Polyelectrolytes
  • Doxorubicin
  • Carboxymethylcellulose Sodium