In Situ Forming Ibuprofen-Grafted Hyperbranched PEG Hydrogels for Sustained Osteoarthritis Treatment

Osteoarthritis (OA) is a common degenerative joint disease characterized by the gradual deterioration and destruction of articular cartilage, accompanied by inflammation and pain, which severely impacts patients' quality of life. Current treatment methods primarily involve non-steroidal anti-inflammatory drugs (NSAIDs), with ibuprofen being widely used for oral administration due to its effective anti-inflammatory and analgesic properties. However, long-term oral administration of ibuprofen can lead to side effects such as gastrointestinal issues. Therefore, developing a controlled-release local drug delivery system is of significant importance.<br/>In this study, we grafted ibuprofen onto hydroxyethyl acrylamide (HEAA) via esterification and then polymerized it with polyethylene glycol diacrylate (PEGDA) using reversible addition–fragmentation chain transfer (RAFT) polymerization, resulting in a high molecular weight polymer with ibuprofen grafts (HBPEG-IBU). Nuclear Magnetic Resonance (NMR) analysis revealed that the synthesized polymer had a high grafting efficiency. Thiolated hyaluronic acid (HA-SH), a modified natural polymer, was employed to form hydrogels with HBPEG-IBU through a Michael addition reaction, creating a hydrogel with in situ gelation capability. Rheological analysis indicated that the hydrogel exhibited favorable mechanical properties.<br/>To evaluate the in vivo stability and drug release profile of the hydrogel, swelling and degradation experiments were conducted at different concentrations of hyaluronidase, along with in vitro release experiments. The results showed that at a hyaluronidase concentration of 1 U/mL, the degradation time of the hydrogel could reach up to 30 days, indicating a long-term sustained-release property. Additionally, the biocompatibility of the materials was confirmed through in vitro experiments, demonstrating that both HBPEG-IBU and the prepared hydrogel exhibited good cell compatibility. Furthermore, an anti-inflammatory experiment using a chondrocyte model verified the hydrogel's significant anti-inflammatory activity. In summary, the HBPEG-IBU hydrogel developed in this study shows potential application value for the local treatment of osteoarthritis.