pH-Responsive Modified HAMA Microspheres Regulate the Inflammatory Microenvironment of Intervertebral Discs

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Regenerative Medicine

Background:

• Intervertebral disc degeneration (IVDD) involves local lactic acid accumulation, decreased pH, and inflammation, disrupting disc homeostasis.
• Current treatments lack targeted drug delivery, necessitating intelligent systems for effective intervention.
• Interleukin-1 receptor antagonist (IL-1 Ra) shows anti-inflammatory potential but suffers from a short biological half-life.

Purpose of the Study:

• To engineer acid-sensitive methacrylated hyaluronic acid (HAMA) microspheres for targeted drug delivery in IVDD.
• To enhance the slow-release properties of IL-1 Ra using bovine serum albumin nanoparticles (BNPs).
• To evaluate the efficacy of modified HAMA microspheres loaded with BNPs (Modified MS) in reversing the inflammatory microenvironment of degenerative nucleus pulposus.

Main Methods:

• Fabrication of acid-sensitive HAMA microspheres using microfluidic technology.
• Loading of IL-1 Ra onto bovine serum albumin nanoparticles (BNPs) to improve its half-life.
• Surface modification of HAMA microspheres via Schiff base chemical bonding for nanoparticle attachment and drug release.
• Assessment of microsphere injectability, porosity, and nanoparticle loading efficiency.

Main Results:

• Successfully constructed acid-sensitive HAMA microspheres capable of intelligent drug release.
• Achieved efficient and uniform loading of BNPs onto HAMA microspheres via Schiff base bonds.
• Demonstrated good injectability and porosity of the modified HAMA microspheres.
• Showed that Modified MS can significantly reverse the inflammatory microenvironment in degenerative nucleus pulposus.

Conclusions:

• Developed a novel targeted drug delivery system using modified HAMA microspheres for IVDD treatment.
• The acid-sensitive nature and enhanced drug retention of Modified MS offer a promising therapeutic strategy.
• This approach holds potential for restoring homeostasis in degenerated intervertebral discs by mitigating inflammation.