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

IF 5.5 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules Pub Date : 2025-07-14 DOI:10.1021/acs.biomac.5c00479

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

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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.

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查看原文本刊更多论文

布洛芬偶联聚赖氨酸甲基丙烯酸酯水凝胶调节巨噬细胞极化和减轻体内炎症。

聚赖氨酸（EPL）因其优异的抗菌活性和良好的生物相容性而广泛应用于生物医学领域。本研究采用碳二亚胺化学方法将水溶性EPL与疏水性药物布洛芬（ibuprofen， IBU）接枝，然后用甲基丙烯酸酐（MA）修饰得到的IBU-EPL偶联物，制备IBU-EPL-MA。IBU-EPL-MA具有良好的光交联性，形成水凝胶，具有药物缓释和良好的血液相容性。显著抑制细菌生长，促进脂多糖（LPS）诱导的巨噬细胞向m2样表型极化，降低体外活性氧（ROS）水平。在小鼠皮下模型中，IBU-EPL-MA水凝胶引起了较轻的异物反应（FBR），证明了纤维囊厚度减少，巨噬细胞极化到m2样表型增加，植入物周围血管形成程度减少。这项研究为多功能epl生物材料的抗菌、抗炎和持续药物释放能力提供了见解，扩大了潜在的生物医学应用。

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来源期刊

Biomacromolecules 化学-高分子科学

CiteScore

10.60

自引率

4.80%

发文量

417

审稿时长

1.6 months

期刊介绍： Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.