Synthesis and characterization of berberine-loaded chitosan nanoparticles for the protection of urethane-induced lung cancer

Int J Pharm. 2022 Apr 25:618:121652. doi: 10.1016/j.ijpharm.2022.121652. Epub 2022 Mar 9.

Abstract

Lung cancer is one of the most common types of malignant tumors of the respiratory system and has the highest rates of incidence and mortality of malignant tumors. This study aimed to synthesize and characterize berberine-loaded chitosan nanoparticles (BBR-COSNPs) and to evaluate their protective effects against urethane-induced lung cancer. Forty male albino mice were divided into four groups, with the first serving as a negative control and the other three groups were injected intraperitoneally with urethane (1 mg/kg b.w) each other day for 1 week then group 2 was served as a positive control, however, groups 3 and 4 were treated orally with a daily dose of BBR or BBR-COSNPs (75 mg/kg b.w) for 10 consecutive weeks. Blood and lung tissue samples are collected for laboratory assay. The BBR-COSNPs were spherical, with an average particle size of 45.56 nm and zeta potential of 39.82 1.82 mV. The in vivo data demonstrated that mice given urethane alone had a significant increase in MDA, NO, NF-κB level, HIF1-α, and COX-2-positive expression in the lung tissue and serum VEGFR2, ALT, AST, urea, and creatinine accompanied with a significant decrease in GSH, SOD, caspase 9 in the lung tissue and serum BAX. Co-treatment with BBR-COSNPs suppressed lung cancer growth and promoted apoptosis by modulating serum BAX and lung caspase 9 gene expressions. In addition, BBR-COSNPs inhibited tumor angiogenesis by reduction in levels of serum VEGFR2 and lung HIF 1 gene expression. It is possible to conclude that BBR-COSNPs can be used in oral administration formulations for lunganticancer therapy.

Keywords: Berberine; Chitosan nanoparticles; Lung cancer; Urethane.

MeSH terms

  • Animals
  • Berberine*
  • Caspase 9
  • Chitosan*
  • Lung Neoplasms* / chemically induced
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / prevention & control
  • Male
  • Mice
  • Nanoparticles*
  • Urethane
  • bcl-2-Associated X Protein

Substances

  • bcl-2-Associated X Protein
  • Berberine
  • Urethane
  • Chitosan
  • Caspase 9