Relaxin-Loaded Inhaled Porous Microspheres Inhibit Idiopathic Pulmonary Fibrosis and Improve Pulmonary Function...

Area of Science:

• Biomedical Engineering
• Pulmonary Medicine
• Drug Delivery Systems

Background:

• Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with no effective etiological treatments.
• Recombinant Human Relaxin-2 (RLX) shows anti-fibrotic properties but requires frequent administration due to its short half-life.
• Developing sustained-release formulations for RLX is crucial for effective IPF therapy.

Purpose of the Study:

• To develop and evaluate porous microspheres loaded with RLX (RLX@PMs) for aerosol inhalation therapy in IPF.
• To assess the long-term drug release, therapeutic efficacy, and safety of RLX@PMs in a preclinical IPF model.
• To investigate the underlying mechanisms of RLX-mediated anti-fibrotic effects.

Main Methods:

• Fabrication of porous microspheres (PMs) encapsulating RLX.
• Characterization of RLX@PMs for drug loading, release kinetics (over 24 days), and structural integrity.
• Evaluation of RLX@PMs in a bleomycin-induced pulmonary fibrosis mouse model following a single aerosol inhalation.
• Assessment of lung function (compliance), collagen deposition, histological changes, and safety compared to pirfenidone.
• In vitro studies on human myofibroblast contraction and macrophage polarization.

Main Results:

• RLX@PMs demonstrated sustained release of active RLX over 24 days.
• A single inhalation of RLX@PMs significantly reduced collagen deposition, improved lung architecture, and restored compliance in mice.
• RLX@PMs exhibited a favorable safety profile compared to pirfenidone.
• RLX inhibited myofibroblast-induced collagen gel contraction and M2 macrophage polarization in vitro.

Conclusions:

• RLX@PMs represent a novel, effective, and potentially safer inhaled therapeutic strategy for IPF.
• The porous microsphere formulation overcomes the pharmacokinetic limitations of RLX, enabling sustained lung delivery.
• These findings suggest significant clinical translational potential for RLX@PMs in treating pulmonary fibrosis.