Artemisinin emulgel ameliorates cartilage degradation in knee osteoarthritis: in vitro and in vivo studies

Ther Deliv. 2024;15(12):939-955. doi: 10.1080/20415990.2024.2418281. Epub 2024 Nov 6.

Abstract

Aim: Laboratory scale-up of artemisinin-loaded emulgel (ART-emulgel) was carried out and characterized for therapeutic performance in osteoarthritis (OA).Materials & methods: The solubility of ART in various oils, surfactants and co-surfactants were screened for construction of pseudo ternary phase diagram (TPD), followed by scale-up of artemisinin loaded nanoemulsion (ART-NE). ART-NE was amalgamated with Carbopol Ultrez 10-NF to prepare ART-emulgel that was later characterized in vitro and in vivo to analyze therapeutic efficacy in monosodium-iodoacetate (MIA) induced knee OA.Results: The droplet diameter of ART-NE was estimated to be 104.3 ± 2.593 nm with a polydispersity index of 0.245 ± 0.019 in addition to ζ-potential of 0.434 ± 0.028 mV. Steady-state flux and permeability coefficient for ART-emulgel were estimated to be 0.651 ± 0.031 µg.cm2/h and 0.245 ± 0.011 cm/h, respectively. ART-emulgel demonstrated 43.18% reduction in COX-2 level; 52.28% drop in IL-1β, and 88.78% alleviation of Tumor Necrosis Factor-α (TNF-α) level when compared with monosodium-iodoacetate induced OA rats. ART-emulgel and injectable ART (intra-articular; I.A) portrayed minor synovial erosion compared with blank and diclofenac emulgel. Histopathological evidences indicated restoration of cartilage integrity followed by reduction of OARSI scores in ART-emulgel when compared with disease control animals.Conclusion: ART-emulgel is a potential dosage form for translating into a clinically viable product for the management of OA.

Keywords: COX-2 expression; artemisinin; emulgel; knee osteoarthritis; proinflammatory cytokines.

Plain language summary

[Box: see text].

MeSH terms

  • Animals
  • Artemisinins* / administration & dosage
  • Artemisinins* / chemistry
  • Artemisinins* / pharmacology
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / pathology
  • Drug Carriers / chemistry
  • Emulsions*
  • Gels
  • Iodoacetic Acid
  • Male
  • Osteoarthritis, Knee* / drug therapy
  • Osteoarthritis, Knee* / metabolism
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Artemisinins
  • Emulsions
  • artemisinin
  • Iodoacetic Acid
  • Gels
  • Drug Carriers