Wenrui Zhang , Hao Zhang , Jinlin He , Xingwei Sun , Mingzu Zhang , Peihong Ni
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引用次数: 0
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.
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.