Cannabidiol-Loaded Solid Lipid Nanoparticles Ameliorate the Inhibition of Proinflammatory Cytokines and Free Radicals in an In Vitro Inflammation-Induced Cell Model

Int J Mol Sci. 2024 Apr 26;25(9):4744. doi: 10.3390/ijms25094744.


Cannabidiol (CBD) is a non-psychoactive compound derived from Cannabis sativa. It has demonstrated promising effects in combating inflammation and holds potential as a treatment for the progression of chronic inflammation. However, the clinical application of CBD is limited due to its poor solubility and bioavailability. This study introduces an effective method for preparing CBD-loaded solid lipid nanoparticles (CBD-SLNs) using a combination of low-energy hot homogenization and ultrasonication. We enhanced this process by employing statistical optimization with response surface methodology (RSM). The optimized CBD-SLN formulation utilizes glyceryl monostearate as the primary lipid component of the nanocarrier. The CBD-SLN formulation is screened as a potential tool for managing chronic inflammation. Stable, uniformly dispersed spherical nanoparticles with a size of 123 nm, a surface charge of -32.1 mV, an encapsulation efficiency of 95.16%, and a drug loading of 2.36% were obtained. The CBD-SLNs exhibited sustained release properties, ensuring prolonged and controlled CBD delivery, which could potentially amplify its therapeutic effects. Additionally, we observed that CBD-SLNs significantly reduced both reactive oxygen and nitrogen species and proinflammatory cytokines in chondrocyte and macrophage cell lines, with these inhibitory effects being more pronounced than those of free CBD. In conclusion, CBD-SLNs demonstrated superiority over free CBD, highlighting its potential as an effective delivery system for CBD.

Keywords: Box–Behnken; cannabidiol; drug delivery; inflammation; response surface methodology; solid lipid nanoparticle.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Cannabidiol* / chemistry
  • Cannabidiol* / pharmacology
  • Cell Line
  • Cytokines* / metabolism
  • Drug Carriers / chemistry
  • Free Radicals
  • Humans
  • Inflammation* / drug therapy
  • Lipids / chemistry
  • Liposomes
  • Mice
  • Nanoparticles* / chemistry
  • Reactive Oxygen Species / metabolism


  • Cannabidiol
  • Cytokines
  • Free Radicals
  • Drug Carriers
  • Lipids
  • Lipid Nanoparticles
  • Reactive Oxygen Species
  • Anti-Inflammatory Agents
  • Liposomes