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Targeted therapy of rheumatoid arthritis via macrophage repolarization

Xu Zhou1, Dandan Huang2, Runkong Wang1

  • 1Sichuan Provincial Orthopedic Hospital, Chengdu, China.

Drug Delivery
|November 12, 2021
PubMed

Insights

This study developed folic acid-modified liposomes carrying triptolide to target M1 macrophages in rheumatoid arthritis. This targeted therapy effectively reduced inflammation and toxicity in rats by repolarizing macrophages.

Area of Science:

  • Immunology
  • Nanomedicine
  • Pharmacology

Background:

  • Macrophage polarization is crucial in rheumatoid arthritis (RA) pathogenesis.
  • M1 macrophages, prevalent in RA, overexpress folate receptors.
  • Targeted delivery systems are needed to modulate macrophage function in RA.

Purpose of the Study:

  • To develop folic acid-modified liposomes (FA-Lips) encapsulating triptolide (TP) for targeted RA therapy.
  • To evaluate the efficacy and safety of FA-Lips/TP in an adjuvant-induced arthritis (AIA) rat model.
  • To investigate the mechanism of macrophage repolarization from M1 to M2 subtypes.

Main Methods:

  • Fabrication and characterization of folic acid-modified liposomes (FA-Lips) encapsulating triptolide (TP).
  • In vitro assessment of liposome internalization in LPS-stimulated RAW 264.7 cells.
  • In vivo evaluation of FA-Lips biodistribution, therapeutic efficacy, and toxicity in an AIA rat model.

Main Results:

  • FA-Lips demonstrated significantly higher cellular uptake than unmodified liposomes.
  • FA-Lips selectively accumulated in the inflamed paws of AIA rats.
  • FA-Lips/TP treatment significantly improved therapeutic outcomes and reduced toxicity in AIA rats by targeting M1 macrophages and promoting M2 repolarization.

Conclusions:

  • Folic acid-modified liposomes offer a promising targeted delivery system for RA therapy.
  • FA-Lips/TP effectively targets M1 macrophages and repolarizes them to an anti-inflammatory M2 phenotype.
  • This approach provides a safe and effective strategy for inflammation-targeted therapy in rheumatoid arthritis.
Keywords:
Rheumatoid arthritisfolate receptorliposomesmacrophage repolarizationtriptolide

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