Synthesis and Characterization of Inhalable Flavonoid Nanoparticle for Lung Cancer Cell Targeting

J Biomed Nanotechnol. 2016 Feb;12(2):371-86. doi: 10.1166/jbn.2016.2162.

Abstract

Current cancer treatments are not adequate to cure cancer disease, as most chemotherapeutic drugs do not differentiate between cancerous and non-cancerous cells; which lead to systemic toxicity and adverse effects. We have developed a promising approach to deliver a potential anti-cancer compound (curcumin) for lung cancer treatment through pulmonary delivery. Three different sizes of curcumin micellar nanoparticles (Cur-NPs) were fabricated and their cytotoxicity effects (proliferation, apoptosis, cell cycle progression) were evaluated against non-small-cell lung cancer, human lung carcinoma (A549) and human lung adenocarcinoma (Calu-3). The in vitro cytotoxicity assay showed that Cur-NPs were more effective to kill lung cancer cells compared to DMSO-solubilised raw curcumin. The potency of the anti-cancer killing activities was size-dependent. Both raw curcumin and Cur-NPs were not toxic to healthy lung cells (BEAS-2B). Smaller Cur-NPs accumulated within nucleus, membrane and cytoplasm. Cur-NPs also induced apoptosis and caused G2/M arrest in both A549 and Calu-3 cell lines. Compared to raw curcumin, Cur-NPs were more effective in suppressing the expression of the inflammatory marker, Interleukin-8 (IL8). The aerosol performance of Cur-NPs was characterized using the next generation impactor (NGI). All Cur-NPs showed promising aerosolization property with mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) ranging between 4.8-5.2 and 2.0-2.1, respectively. This study suggests that inhaled curcumin nanoparticles could potentially be used for lung cancer treatment with minimal side effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Curcumin / pharmacology
  • Curcumin / therapeutic use
  • Endocytosis / drug effects
  • Flavonoids / pharmacology
  • Flavonoids / therapeutic use*
  • Humans
  • Interleukin-8 / metabolism
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Nanoparticles / chemistry*
  • Nanoparticles / toxicity
  • Nanoparticles / ultrastructure
  • Nebulizers and Vaporizers
  • Particle Size
  • Povidone / chemistry

Substances

  • Flavonoids
  • Interleukin-8
  • Povidone
  • Curcumin