Liu Yuheng, Guo Chuan, Wang Yu, Kong Qing-Quan
Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, No. 37, Guoxue Road, Chengdu 610041, China.
Biomacromolecules. 2025 Jan 13;26(1):209-221. doi: 10.1021/acs.biomac.4c00965. Epub 2024 Dec 13.
Intervertebral disc degeneration is characterized by a localized, chronic inflammatory response leading to a synthesis/catabolism imbalance within the nucleus pulposus (NP) and progressive functional impairment within the NP. Polyphenol molecules have been widely used in anti-inflammatory therapies in recent years; therefore, we designed an injectable, temperature-sensitive hydrogel PLGA-PEG-PLGA-based drug delivery system for local and sustained delivery of two drugs tannic acid (TA) and resveratrol (Res), with the hydrogel carrying TA directly and Res indirectly (carried directly by inflammation-responsive nanoparticles). The delivery system presents good injectability at room temperature and forms a gel in situ upon entering the intervertebral disc. The delivery system can rapidly release TA and sustain Res release. In vitro and in vivo experiments have shown that this hydrogel drug delivery system is effective in anti-inflammation of degenerated intervertebral discs and promotes the regeneration of extracellular matrix in the NP.
椎间盘退变的特征是局部慢性炎症反应,导致髓核(NP)内合成/分解代谢失衡以及NP内渐进性功能损害。近年来,多酚分子已广泛用于抗炎治疗;因此,我们设计了一种基于可注射、温度敏感水凝胶PLGA-PEG-PLGA的药物递送系统,用于局部和持续递送两种药物——单宁酸(TA)和白藜芦醇(Res),该水凝胶直接携带TA,间接携带Res(由炎症响应纳米颗粒直接携带)。该递送系统在室温下具有良好的可注射性,进入椎间盘后可原位形成凝胶。该递送系统可快速释放TA并持续释放Res。体外和体内实验表明,这种水凝胶药物递送系统对退变椎间盘的抗炎有效,并促进NP中细胞外基质的再生。