Ibuprofen Conjugated Epsilon-poly-l-lysine Methacrylate Hydrogel Modulates Macrophage Polarization and Mitigates Inflammation In Vivo

Yifan Lu; Bo Chen; Xiangxin Lou; Yi Li; Jinglei Wu; Haochen Yao; Bei Feng

doi:10.1021/acs.biomac.5c00479

Ibuprofen Conjugated Epsilon-poly-l-lysine Methacrylate Hydrogel Modulates Macrophage Polarization and Mitigates Inflammation In Vivo

Biomacromolecules. 2025 Jul 1. doi: 10.1021/acs.biomac.5c00479. Online ahead of print.

Authors

Yifan Lu^{1

2}, Bo Chen³, Xiangxin Lou², Yi Li^{1

2}, Jinglei Wu², Haochen Yao⁴, Bei Feng^{1

5}

Affiliations

¹ Heart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P. R. China.
² Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, P. R. China.
³ Laboratory of Advanced Theranostic Materials and Technology, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, P. R. China.
⁴ Key Laboratory and Engineering Laboratory of Lymphatic Surgery Jilin Province, China-Japan Union Hospital of Jilin University, Changchun 130033, P. R. China.
⁵ Shanghai Clinical Research Center for Rare Pediatric Diseases, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P. R. China.

PMID: 40598882
DOI: 10.1021/acs.biomac.5c00479

Abstract

Epsilon-poly-l-lysine (EPL) is widely used in many biomedical applications due to its excellent antibacterial activity and good biocompatibility. In this study, we report an approach of carbodiimide chemistry to graft water-soluble EPL with hydrophobic drug ibuprofen (IBU) and then modify the obtained IBU-EPL conjugate with methacrylic anhydride (MA) to prepare IBU-EPL-MA. The IBU-EPL-MA was of good photo-cross-linkability to form hydrogel with sustained drug release and good blood compatibility. It significantly inhibited bacterial growth, promoted lipopolysaccharide (LPS)-induced macrophage polarization to the M2-like phenotype, and reduced reactive oxygen species (ROS) levels in vitro. The IBU-EPL-MA hydrogel elicited milder foreign body response (FBR) as evidenced by reduced fibrous capsule thickness, increased macrophage polarization to M2-like phenotype, and less extent of blood vessel formation surrounding implants in a mouse subcutaneous model. This study provides insights into multifunctional EPL-based biomaterials with antibacterial, anti-inflammatory, and sustained drug release capabilities that expand potential biomedical applications.