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Paeoniflorin-loaded pH-sensitive liposomes alleviate synovial inflammation by altering macrophage polarity via STAT

Dongyi Wang1, Fan Yang1, Wei Shang2

  • 1Nanjing University of Chinese Medicine, 210023 Nanjing, China; Department of Integrated Traditional and Western Medicine, Jinling Hospital, School of Medicine, Nanjing University, 210002 Nanjing, China.

International Immunopharmacology
|November 8, 2021
PubMed

Insights

Paeoniflorin-loaded liposomes (Pae-LS) enhance rheumatoid arthritis (RA) treatment by improving paeoniflorin delivery and regulating macrophage polarization. Pae-LS effectively reduce synovial inflammation in rats, showing potential for RA therapy.

Area of Science:

  • Immunology
  • Pharmacology
  • Biotechnology

Background:

  • Macrophage polarization is crucial in rheumatoid arthritis (RA) pathogenesis.
  • Paeoniflorin (Pae) shows therapeutic potential but suffers from low bioavailability.
  • Novel drug delivery systems are needed to enhance Pae's efficacy for RA treatment.

Purpose of the Study:

  • To develop folate and PEG co-conjugated paeoniflorin-loaded liposomes (Pae-LS).
  • To evaluate the biophysical properties, macrophage uptake, and therapeutic effects of Pae-LS in a collagen-induced arthritis (CIA) rat model.
  • To investigate the mechanism of Pae-LS in modulating macrophage polarization and synovial inflammation.

Main Methods:

  • Preparation and characterization of Pae-LS, including physical stability, release kinetics, and pH-responsiveness.
  • Assessment of Pae-LS uptake by RAW 264.7 macrophages.
  • In vivo evaluation in CIA rats, measuring synovial inflammation, hyperplasia, and cytokine levels.
  • Analysis of STAT signaling pathways (STAT1 and STAT6) involved in macrophage polarization.

Main Results:

  • Pae-LS exhibited favorable physical stability, sustained release, long circulation, and pH-responsive properties.
  • Pae-LS demonstrated significantly higher uptake by activated macrophages compared to free Pae.
  • Pae-LS treatment effectively repressed pro-inflammatory cytokine production (IL-1β, IL-6, TNF-α) and iNOS expression by inhibiting STAT1 phosphorylation.
  • Pae-LS promoted anti-inflammatory cytokine (IL-10) production and M2 macrophage markers (CD206) via enhanced p-STAT6 signaling.
  • Pae-LS significantly alleviated synovial inflammation and hyperplasia in CIA rats.

Conclusions:

  • Folate and PEG co-conjugated Pae-LS represent an effective liposome delivery system for enhancing paeoniflorin's therapeutic benefits in RA.
  • Pae-LS modulate macrophage polarization through STAT signaling pathways, suppressing synovial inflammation in CIA rats.
  • Pae-LS hold significant potential as a novel therapeutic strategy for rheumatoid arthritis treatment.
Keywords:
LiposomeMacrophagesPaeoniflorinRheumatoid arthritisSTAT signaling

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