Doxorubicin and 4-nitrochalcone loaded in beeswax-based nanostructured lipid carriers: In vitro antitumoral screening and evaluation of synergistic effect on HepG-2 cells

Int J Pharm. 2024 Dec 5:666:124788. doi: 10.1016/j.ijpharm.2024.124788. Epub 2024 Oct 3.

Abstract

Cancer is the second most deadly disease worldwide, and the most traditional approaches such as chemotherapy still face limitations associated to drug dosage and off-target side effects. To address these issues, we propose the simultaneous administration of 4-Nitrochalcone (4NC) and Doxorubicin (DOX) using beeswax based nanostructured lipid carriers (NLCs). The co-encapsulation of 4NC and DOX in the beeswax based NLCs was performed using the water/oil/water double emulsion technique in association with the melt dispersion approach. The system composed by semi-spherical NLCs with an average diameter around 200 nm and narrow size distribution, displayed colloidal stability before and after redispersion, keeping the zeta potential below -30 mV. The antitumor activity of the nanoparticles was screened on different tumor cell lines, and the induced cellular death and internal ROS levels were analyzed on hepatocarcinoma cells, which were found to be more affected by the combination of 4NC and DOX. The results indicated that 4NC + DOX-NCLs could promote cytotoxicity and oxidative damage-mediated apoptosis in a HepG-2 cell line.

Keywords: 4-Nitrochlacone; Doxorubicin; Drug Delivery; Hepatocarcinoma; Lipid Nanoparticles; Synergism.

MeSH terms

  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / pharmacology
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis* / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chalcones / administration & dosage
  • Chalcones / chemistry
  • Chalcones / pharmacology
  • Doxorubicin* / administration & dosage
  • Doxorubicin* / chemistry
  • Doxorubicin* / pharmacology
  • Drug Carriers* / chemistry
  • Drug Synergism*
  • Hep G2 Cells
  • Humans
  • Lipids* / chemistry
  • Nanoparticles / chemistry
  • Nanostructures* / chemistry
  • Particle Size
  • Reactive Oxygen Species* / metabolism
  • Waxes* / chemistry

Substances

  • Doxorubicin
  • beeswax
  • Waxes
  • Drug Carriers
  • Lipids
  • Reactive Oxygen Species
  • Chalcones
  • Antineoplastic Agents
  • Antibiotics, Antineoplastic