Xanthan gum-based protocatechuic acid grafted carboxymethyl chitosan hydrogel with injectable, spraying, self-healing, and enhanced antioxidant properties.

Jiaxue Tang, Chuzhou Wen, Shengnan Zheng, Changkai Sun, Fengtao Wang, Shui Guan
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Abstract

Overcoming the limitations of conventional antioxidants in treating oxidative stress-related neurodegenerative diseases (NDs) remains a critical challenge, thus more effective antioxidant strategies need to be studied urgently. To address this, we developed a novel pH-responsive drug-delivery hydrogel, PCA-g-CMCS/OXG, by grafting protocatechuic acid (PCA) onto carboxymethyl chitosan (CMCS) via amide bonds and blending it with oxidized xanthan gum (OXG) to form dynamic imine bonds. The conjugate PCA-g-CMCS achieved an unprecedented grafting efficiency of 785.3 mg g-1through optimized reactant ratios, pH, and reaction time. And the multifunctional hydrogel PCA-g-CMCS/OXG offers three key advantages: (1) rapid tunable gelation time (10-110 s) and robust mechanical/rheological properties enabling injectable and sprayable applications; (2) self-healing capability and sustained pH-responsive PCA release over 15 d, ensuring long-term therapeutic efficacy; and (3) superior cytoprotection, as the hydrogel exhibited excellent biocompatibility with SH-SY5Y neuronal cells and significantly increased cell viability to 76.60% from H2O2-induced oxidative damage (vs. 48.61% for control,p< 0.01). Therefore, the smart Schiff's base hydrogel is a drug loaded material with great clinical application prospect for the treatment of NDs.

黄原胶基原儿茶酸接枝羧甲基壳聚糖水凝胶具有可注射性、喷雾性、自愈性和增强的抗氧化性能。
克服传统抗氧化剂治疗氧化应激相关神经退行性疾病的局限性仍然是一个严峻的挑战,因此迫切需要研究更有效的抗氧化剂策略。为了解决这一问题,我们通过酰胺键将原儿茶酸(PCA)接枝到羧甲基壳聚糖(CMCS)上,并与氧化黄原胶(OXG)混合形成动态亚胺键,开发了一种新的ph响应型药物递送水凝胶PCA-g-CMCS/OXG。通过优化反应物配比、pH和反应时间,共轭PCA-g-CMCS的接枝效率达到了前所未有的785.3 mg/g。多功能水凝胶PCA-g-CMCS/OXG具有三个关键优势:(1)快速可调凝胶时间(10-110秒)和强大的机械/流变特性,可注射和喷涂;(2)自愈能力和持续的ph响应性PCA释放超过15天,确保长期治疗效果;(3)具有良好的细胞保护作用,水凝胶与SH-SY5Y神经元细胞具有良好的生物相容性,h2o2诱导的氧化损伤细胞存活率显著提高至76.60%(对照组为48.61%,p < 0.01)。因此,智能希夫碱水凝胶是治疗神经退行性疾病极具临床应用前景的载药材料。
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