Preparation and characterization of amoxapine- and naringin-loaded solid lipid nanoparticles: drug-release and molecular-docking studies

Nanomedicine (Lond). 2022 Dec;17(28):2133-2144. doi: 10.2217/nnm-2022-0167. Epub 2023 Feb 14.

Abstract

Aim: Amoxapine (AMX) has been reported to be metabolized by CYP3A4 and CYP2D6. Naringin (NG) has been reported to inhibit CYP enzymes. Therefore, the current work was designed to develop AMX solid lipid nanoparticles (AMX-SLNs) and NG-SLNs for better therapeutic performance. Materials & methods: AMX-SLNs and NG-SLNs were prepared and characterized. AMX and NG interactions with CYP450s were studied with molecular docking to rationalize the effectiveness of the combination. Results: AMX-SLNs and NG-SLNs showed nanometric size with a sustained in vitro drug-release profile. NG showed a higher predicted binding affinity for CYP3A4 and CYP2D6, suggesting the potential for inhibition. Conclusion: The developed formulations were thoroughly characterized along with molecular docking data indicating promising AMX and NG combinations that may show good therapeutic activity.

Keywords: CYP450; DSC and XRD analysis; controlled drug release; cost–effectiveness; lipid-based nanoparticles; metabolism; nanoparticles; pharmacokinetic; simultaneous analysis.

MeSH terms

  • Amoxapine*
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 CYP3A
  • Drug Carriers / chemistry
  • Lipids / chemistry
  • Molecular Docking Simulation
  • Nanoparticles* / chemistry
  • Particle Size

Substances

  • Lipid Nanoparticles
  • naringin
  • Amoxapine
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 CYP3A
  • Lipids
  • Drug Carriers