Intra-articular Histone Deacetylase Inhibitor Microcarrier Delivery to Reduce Osteoarthritis

Nano Lett. 2023 Dec 13;23(23):10832-10840. doi: 10.1021/acs.nanolett.3c03037. Epub 2023 Nov 27.

Abstract

The histone deacetylase inhibitor (HDACi) was a milestone in the treatment of refractory T-cell lymphoma. However, the beneficial effects of HDACi have not been appreciated in osteoarthritis (OA). Herein, we implemented a microcarrier system because of the outstanding advantages of controlled and sustained release, biodegradability, and biocompatibility. The poly(d,l-lactide-co-glycolide) (PLGA) microcapsules have a regulated and sustained release profile with a reduced initial burst release, which can improve the encapsulation efficiency of the Chidamide. The emulsion solvent evaporation strategy was used to encapsulate Chidamide in PLGA microcapsules. The encapsulation of Chidamide was established by UV-vis spectra and scanning electron microscopy. Additionally, the inhibition of Tnnt3 and immune stimulation by Chidamide helped to inhibit cartilage destruction and prevent articular cartilage degeneration. Based on the results, the Chidamide in PLGA microcapsules provides a transformative therapeutic strategy for the treatment of osteoarthritis patients to relieve symptoms and protect against cartilage degeneration.

Keywords: Chidamide; PLGA; histone deacetylase inhibitor; microcarrier; osteoarthritis.

MeSH terms

  • Capsules
  • Delayed-Action Preparations / therapeutic use
  • Histone Deacetylase Inhibitors* / pharmacology
  • Histone Deacetylase Inhibitors* / therapeutic use
  • Humans
  • Osteoarthritis* / drug therapy

Substances

  • N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide
  • Histone Deacetylase Inhibitors
  • Delayed-Action Preparations
  • Capsules