Polyketal Nanoparticles Co-Loaded With miR-124 and Ketoprofen for Treatment of Rheumatoid Arthritis

J Pharm Sci. 2021 May;110(5):2233-2240. doi: 10.1016/j.xphs.2021.01.024. Epub 2021 Jan 29.

Abstract

Ketoprofen, a non-steroidal anti-inflammatory drug, can effectively relieve pain associated with arthritis, and microRNA-124 (miR-124) can inhibit the progression of the disease. In this study, poly (cyclohexane-1,4-diylacetone dimethylene ketal) (PCADK) nanoparticles (NPs) co-loaded with ketoprofen and miR-124 were successfully prepared using an emulsified solvent evaporation method. The co-loaded NPs exhibited a mean particle diameter of 160 nm. The acid sensitivity of the NPs was determined through in vitro release experiments. An adjuvant-induced arthritis rat model of arthritis was established for evaluating the pharmacodynamics of the NPs through clinical scoring and degree of swelling. The PCADK NPs exhibited more potent pharmacodynamic effects owing to the acid-sensitive properties of the carrier materials, compared with Poly (lactic-co-glycolic acid) (PLGA) NPs. Furthermore, PCADK co-loaded NPs exhibited superior anti-inflammatory effects compared to NPs loaded with either miR-124 or ketoprofen alone. In conclusion, co-delivery of ketoprofen and miR-124 through NPs is a promising strategy for the treatment of arthritis.

Keywords: Co-delivery; Ketoprofen; Nanoparticles; PCADK; Rheumatoid arthritis; microRNA-124.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Rheumatoid* / drug therapy
  • Drug Carriers / therapeutic use
  • Ketoprofen* / therapeutic use
  • MicroRNAs*
  • Nanoparticles*
  • Particle Size
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rats

Substances

  • Drug Carriers
  • MIRN124 microRNA, rat
  • MicroRNAs
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Ketoprofen