Minimally invasive, sustained-release relaxin-2 microparticles reverse arthrofibrosis

Area of Science:

• Biotherapeutics
• Drug Delivery Systems
• Musculoskeletal Diseases

Background:

• Musculoskeletal diseases, particularly arthrofibrosis, lack effective biotherapeutics due to biomechanical complexity and fibrotic tissue accumulation.
• Current treatments for arthrofibrosis, including surgery, do not address the disease's underlying etiology and often fail to restore joint range of motion (ROM).
• Human relaxin-2 (RLX) shows promise as an antifibrotic agent but has faced pharmacokinetic challenges in clinical trials.

Purpose of the Study:

• To design and characterize a novel drug delivery system for sustained, localized release of human relaxin-2 (RLX).
• To evaluate the efficacy of RLX-loaded microparticles in a rat model of arthrofibrosis.
• To assess the translational potential of RLX for treating musculoskeletal fibrosis.

Main Methods:

• Development and in vitro characterization of polymeric microparticles for sustained RLX release.
• Intraarticular administration of RLX-loaded microparticles in a rat model of atraumatic arthrofibrosis.
• Assessment of joint ROM, architecture, and localized/systemic RLX concentrations.

Main Results:

• Polymeric microparticles demonstrated sustained RLX release over multiple weeks without compromising peptide structure or bioactivity.
• Intraarticular administration in rats achieved prolonged, localized RLX concentrations with reduced systemic exposure.
• A single injection of RLX-loaded microparticles successfully restored joint ROM and architecture in the arthrofibrosis model.

Conclusions:

• Sustained, localized delivery of RLX via microparticles effectively treats arthrofibrosis in a preclinical model.
• This approach overcomes previous pharmacokinetic limitations of RLX, suggesting significant clinical translational potential.
• Targeted administration of RLX, confirmed by RXFP1 receptor expression in human tissues, offers a promising therapeutic strategy for musculoskeletal fibrosis.