Triple-Tailored Analgesic Hydrogel System Targeting ADAM17 in Orofacial Inflammatory Pain.

IF 10 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Yingyu Yi, Yuxuan Wu, Yanghong Xu, Zhengjie Han, Yuzhuo Wang, Jianwen Gong, Yubin Hu, Xinzhao Mai, Weizhe Sheng, Junting Li, Yujie Chen, Zhi Yang, Yaqin Zhu
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Abstract

Orofacial inflammatory pain (OFP) is challenging to manage due to its high incidence, complex anatomy, and multifactorial etiology. To address this, a three-step customized therapeutic system is proposed for prolonged pain relief and efficient local drug delivery. First, ADAM17 is identified as a novel therapeutic target for OFP, and find a small-molecule inhibitor, TAPI-1, which can effectively suppress ADAM17 activity. Subsequently, guided by the presence of an amine group on TAPI-1, an optimized hydrogel matrix is synthesized via Schiff-base bonding to enable stable encapsulation. The hydrogel, composed of hyaluronic acid derivatives carrying aldehyde (HAALD) and aminated gelatin (AGel), forms a scaffold that slows drug release. Second, for clinical application in orofacial tissue, unmodified hyaluronic acid (HA) and gelatin are incorporated to optimize the hydrogel's rheological properties for practicable injection. Third, to further prolong drug release, customized hollow mesoporous silica nanoparticles are added to trap a portion of TAPI-1, matching the drug's molecular diameter. This triple-tailored sustained-release hydrogel (HHGA hydrogel) maintains effective drug levels for 7 days, aligning with the pain phase and obviously relieving pain in mice. This "drug-device" innovation exemplifies the potential of personalized medicine in pain management and targeted therapies in translational medicine.

靶向ADAM17的三重定制镇痛水凝胶系统治疗口腔面部炎症性疼痛。
由于其高发病率、复杂的解剖结构和多因素病因,口腔面部炎症性疼痛(OFP)的治疗具有挑战性。为了解决这个问题,提出了一个三步定制治疗系统,以延长疼痛缓解和有效的局部给药。首先,确定ADAM17为OFP的新治疗靶点,并找到一种可有效抑制ADAM17活性的小分子抑制剂TAPI-1。随后,在TAPI-1上存在胺基的引导下,通过希夫碱键合合成了优化的水凝胶基质,以实现稳定的封装。水凝胶由携带醛的透明质酸衍生物(HAALD)和氨基明胶(AGel)组成,形成减缓药物释放的支架。其次,在口腔面部组织的临床应用中,加入未修饰的透明质酸(HA)和明胶,以优化水凝胶的流变性能,以便于实际注射。第三,为了进一步延长药物释放时间,添加定制的中空介孔二氧化硅纳米颗粒来捕获一部分与药物分子直径相匹配的TAPI-1。该三重定制缓释水凝胶(HHGA水凝胶)维持有效药物水平7天,与疼痛期一致,明显缓解小鼠疼痛。这种“药物装置”创新体现了个性化医疗在疼痛管理和转化医学靶向治疗方面的潜力。
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来源期刊
Advanced Healthcare Materials
Advanced Healthcare Materials 工程技术-生物材料
CiteScore
14.40
自引率
3.00%
发文量
600
审稿时长
1.8 months
期刊介绍: Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.
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