Cisplatin-Loaded Polybutylcyanoacrylate Nanoparticles with Improved Properties as an Anticancer Agent

Int J Mol Sci. 2019 Mar 27;20(7):1531. doi: 10.3390/ijms20071531.

Abstract

This study aims to improve the cytotoxicity and potency of cisplatin-loaded polybutylcyanoacrylate (PBCA) nanoparticles (NPs) for the treatment of lung cancer through the modulation of temperature and polyethylene glycol (PEG) concentration as effective factors affecting the NPs' properties. The NPs were synthesized using an anionic polymerization method and were characterized in terms of size, drug loading efficiency, drug release profile, cytotoxicity effects, drug efficacy, and drug side effects. In this regard, dynamic light scattering (DLS), scanning electron microscopy (SEM), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) methods, and hematoxylin and eosin (H&E) staining were used. The results showed that the size and the drug loading efficiency of the synthesized spherical NPs were 355–386 nm and 14–19%, respectively. Also, the drug release profile showed a controlled and slow drug release pattern with approximately 10% drug release over 48 h. In addition, the NPs significantly increased the cytotoxicity of the cisplatin in vitro environment by approximately 2 times and enhanced the therapeutic effects of the drug in vivo environment by increasing the survival time of lung-cancer-bearing mice by 20% compared to the standard drug receiver group. Also, the nanoformulation decreased the drug toxicity in an in vivo environment. According to the results, increasing the temperature and PEG concentration improved the properties of the drug loading efficiency, drug release profile, and cytotoxicity effect of drug-loaded NPs. Consequently, the synthesized formulation increased the survival of tumor-bearing mice and simultaneously decreased the cisplatin toxicity effects. In conclusion, the prepared nanoformulation can be considered a promising candidate for further evaluation for possible therapeutic use in the treatment of lung cancer.

Keywords: cisplatin; histological study; lung cancer; polybutylcyanoacrylate; polyethylene glycol; temperature.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Cisplatin / therapeutic use
  • Drug Compounding
  • Drug Liberation
  • Enbucrilate / chemistry*
  • Inhibitory Concentration 50
  • Kidney / drug effects
  • Kidney / pathology
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology
  • Male
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Particle Size
  • Static Electricity
  • Tumor Burden

Substances

  • Antineoplastic Agents
  • Enbucrilate
  • Cisplatin