Luo Wanhe, Jiang Yongtao, Liu Jinhuan, Ju Mujie, Algharib Samah Attia, Dawood Ali Sobhy
College of Animal Science and Technology, Tarim University, Alar, Xinjiang 843300, China.
College of Animal Science and Technology, Tarim University, Alar, Xinjiang 843300, China.
Int J Biol Macromol. 2023 Dec 31;253(Pt 6):127248. doi: 10.1016/j.ijbiomac.2023.127248. Epub 2023 Oct 5.
In this study, enrofloxacin (ENR) was encapsulated by oxidized hyaluronic acid (OHA) containing aldehyde groups and chitosan oligosaccharide (COS) containing amino groups through Schiff's base reaction to achieve on-demand release in the micro-environment (pH 5.5 and HAase) of bacterial-infected wounds (Escherichia coli and Staphylococcus aureus). The formation mechanism, physicochemical characterization, responsive release performance, in vitro and in vivo antimicrobial activities, and in vivo regeneration in full-thickness wounds in a bacterial-infected mouse model of the ENR nanogels were systematically studied. According to the single-factor experiment and Design-Expert software, the optimized formula was 3.8 mg/ml COS, 0.5 mg/ml OHA, and 0.3 mg/ml ENR, respectively. The mean particle diameter, polydispersity index, zeta potential, loading capacity, and encapsulation efficiency were 35.6 ± 1.7 nm, -6.7 ± 0.5 mV, 0.25 ± 0.02, 30.4 % ± 1.3 %, and 76.3 % ± 2.6 %, respectively. The appearance, optical microscopy images, SEM, TEM, PXRD, and FTIR showed that the ENR nanogels were successfully prepared. The ENR nanogels exhibited obvious pH and HAase-responsiveness by swelling ratios and in vitro release and had stronger antibacterial activity with time-dependent and concentration-dependent effects, as well as accelerating infected wound healing. In vitro and in vivo biosafety studies suggested the great promise of ENR nanogels as biocompatible wound dressings for infected wounds.
在本研究中，恩诺沙星（ENR）通过席夫碱反应被含有醛基的氧化透明质酸（OHA）和含有氨基的壳寡糖（COS）包裹，以实现在细菌感染伤口（大肠杆菌和金黄色葡萄球菌）的微环境（pH 5.5和透明质酸酶）中按需释放。系统研究了ENR纳米凝胶的形成机制、物理化学表征、响应释放性能、体外和体内抗菌活性以及在细菌感染小鼠模型的全层伤口中的体内再生情况。根据单因素实验和Design-Expert软件，优化配方分别为3.8 mg/ml COS、0.5 mg/ml OHA和0.3 mg/ml ENR。平均粒径、多分散指数、zeta电位、载药量和包封率分别为35.6±1.7 nm、-6.7±0.5 mV、0.25±0.02、30.4%±1.3%和76.3%±2.6%。外观、光学显微镜图像、扫描电子显微镜、透射电子显微镜、粉末X射线衍射和傅里叶变换红外光谱表明成功制备了ENR纳米凝胶。ENR纳米凝胶通过溶胀率和体外释放表现出明显的pH和透明质酸酶响应性，具有较强的抗菌活性，呈现时间依赖性和浓度依赖性效应，并且能加速感染伤口愈合。体外和体内生物安全性研究表明ENR纳米凝胶作为感染伤口的生物相容性伤口敷料具有很大的应用前景。
