Dual-drug-loaded complex hydrogel dressing composed of oxidized hyaluronic acid and modified mesoporous silica for diabetes foot wounds

IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Wenrui Zhang , Hao Zhang , Jinlin He , Xingwei Sun , Mingzu Zhang , Peihong Ni
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Abstract

Hyaluronic acid (HA) has good biocompatibility and significant therapeutic effects in wound healing. However, for the treatment of diabetes wounds, enhancing the strength, antibacterial and multifunctional healing properties of hydrogel dressings based on HA to make them easy to use is still the focus of attention. Herein, we report a hybrid hydrogel dressing composed of oxidized hyaluronic acid (OHA), mesoporous silica loaded with tetracycline, and metformin for the repair of diabetic foot ulcers. HA was first oxidized by using the oxidizing agent sodium periodate to yield OHA containing aldehyde groups (-CHO) in the side chain. Next, amino-modified mesoporous silica (MSN-NH2) was synthesized by a one-step method, and MSN-NH2 was loaded with tetracycline (TH) to obtain MSN-NH2-TH nanoparticles. Finally, OHA, branched polyethyleneimine (bPEI, as crosslinking agent), MSN-NH2-TH, and metformin (Met) were mixed and subjected to a Schiff base reaction to form the dual-drug-loaded complex hydrogel (OP@MSN-TH/Met) containing 35.6% TH in situ. The structures of the synthesized OHA and MSN-NH2 were characterized by FT-IR spectroscopy. The rheological properties and adhesiveness of the hydrogels with different components were investigated. The results of in vitro drug release, antibacterial, and biocompatibility experiments all demonstrated that the complex hydrogel has good performance. Among them, the result of in vitro drug release indicated that the hydrogel has pH-responsive properties. It rapidly releases most of metformin from cross-linked nanoparticles, while simultaneously achieving sustained and slow release of tetracycline. This dual-release mechanism achieves antibacterial and anti-inflammatory effects, ensuring that the whole process of diabetic wound healing is free from bacterial infection. In addition, the diabetes mouse model experiment showed that the wound-closure rate of mice reached 96.6% on the 12th day, indicating that the hydrogel dressing has a good therapeutic effect.

Abstract Image

由氧化透明质酸和改性介孔二氧化硅组成的双药复合水凝胶敷料用于糖尿病足部伤口
透明质酸(HA)具有良好的生物相容性,在伤口愈合中具有显著的治疗作用。然而,对于糖尿病伤口的治疗,增强基于透明质酸的水凝胶敷料的强度、抗菌和多功能愈合性能,使其易于使用仍然是人们关注的焦点。在此,我们报道了一种由氧化透明质酸(OHA)、负载四环素的介孔二氧化硅和二甲双胍组成的混合水凝胶敷料用于修复糖尿病足溃疡。首先用氧化剂高碘酸钠氧化HA,得到侧链上含有醛基(-CHO)的OHA。下一步,通过一步法合成氨基修饰介孔二氧化硅(MSN-NH2),并在MSN-NH2上负载四环素(TH),得到MSN-NH2-TH纳米颗粒。最后,将OHA、支链聚乙烯亚胺(bPEI,作为交联剂)、MSN-NH2-TH和二甲双胍(Met)混合,进行席夫碱反应,形成原位含35.6% TH的双药复合水凝胶(OP@MSN-TH/Met)。用红外光谱对合成的OHA和MSN-NH2的结构进行了表征。研究了不同组分水凝胶的流变性能和粘附性。体外释药、抗菌、生物相容性实验结果均表明该复合水凝胶具有良好的性能。其中体外释药结果表明该水凝胶具有ph响应特性。它从交联纳米颗粒中快速释放大部分二甲双胍,同时实现四环素的持续和缓慢释放。这种双重释放机制达到了抗菌和抗炎的作用,保证了糖尿病伤口愈合的整个过程没有细菌感染。另外,糖尿病小鼠模型实验显示,小鼠第12天伤口愈合率达到96.6%,说明水凝胶敷料具有良好的治疗效果。
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来源期刊
CiteScore
8.00
自引率
8.00%
发文量
879
审稿时长
94 days
期刊介绍: The Journal of Drug Delivery Science and Technology is an international journal devoted to drug delivery and pharmaceutical technology. The journal covers all innovative aspects of all pharmaceutical dosage forms and the most advanced research on controlled release, bioavailability and drug absorption, nanomedicines, gene delivery, tissue engineering, etc. Hot topics, related to manufacturing processes and quality control, are also welcomed.
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