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

Abstract

Currently, intervertebral disc (IVD) degeneration is believed to lead to local accumulation of lactic acid in the IVD, a decrease in pH, activation of the inflammatory pathway, and continued destruction of homeostasis of the IVD. To address these issues, the intelligent and accurate release of drugs is particularly important. In this study, acid-sensitive release methacrylated hyaluronic acid (HAMA) microspheres were constructed by using microfluidic technology, which can be used as a targeted drug delivery system for intervertebral disc degeneration (IVDD) through Schiff base chemical bonding on the surface of the microspheres to achieve intelligent drug release. Interleukin-1 receptor antagonist (IL-1 Ra) is a naturally occurring anti-inflammatory antagonist of the interleukin-1 family of pro-inflammatory cytokines. Despite its outstanding broad-spectrum anti-inflammatory effects, IL-1 Ra has a short biological half-life (4−6 h). The slow-release performance of IL-1 Ra can be greatly improved using bovine serum albumin nanoparticles (BNP). In addition, the modified HAMA microspheres exhibited good injectability and porosity, and efficient and uniform loading of nanoparticles was achieved via the Schiff base bond. The inflammatory microenvironment can be significantly reversed by transporting the modified HAMA microspheres-BNPs (Modified MS) to the degenerative nucleus pulposus.