桧木醇/纳米氧化锌/聚己内酯/聚乙二醇纳米纤维促进耐甲氧西林金黄色葡萄球菌伤口感染的愈合

Beta-thujaplicin/ZnO nanoparticles/polycaprolactone/poly(ethylene glycol) nanofibers promotes healing of wounds with methicillin-resistant Staphylococcus aureus infection

目的制备桧木醇/纳米氧化锌/聚己内酯/聚乙二醇(beta-thujaplicin/zinc oxide nanoparticles/polycaprolactone/polyethylene glycol,β-T/ZnONPs/PCL/PEG)纳米纤维,并评价其对小鼠伤口感染耐甲氧西林金黄色葡萄球菌(methicillin-resistant staphylococcus aureus,MRSA)的治疗作用。方法通过静电纺丝技术制备纳米纤维后,用扫描电镜观察纳米纤维结构,采用傅里叶变换红外光谱仪考察纳米纤维和药物之间的结构和化学键,差示扫描量热仪测定纳米纤维的热力学性质;并采用稀释法测定纳米纤维的体外抗菌活性,MTT实验检测细胞毒性,选择BALB/c小鼠建立MRSA感染的伤口模型,考察纳米纤维的治疗作用。结果 1%β-T/0. 25%ZnONPs/PCL/PEG纳米纤维的直径为(255. 98±56. 08)nm,药物与载体材料之间的相容性较好。0. 5%β-T/0. 5%ZnONPs/PCL/PEG与1%β-T/0. 25%ZnONPs/PCL/PEG两种组分的纳米纤维对MRSA抗菌活性(P> 0. 05)和细胞毒性(P> 0. 05)相似,符合GB/T16886. 5-2011对生物材料的相关标准。动物实验结果显示,在建立伤口给予纳米纤维治疗的第7、11、15天,所有载药组对MRSA引起的伤口感染与裸露组、未载药纳米纤维组相比,具有较好的治疗作用(P <0. 05),在第11天,β-T/ZnONPs/PCL/PEG纳米纤维组伤口愈合率优于其他各组(P <0. 05)。通过病理学观察发现,制备的β-T/ZnONPs/PCL/PEG纳米纤维在促进感染性伤口愈合方面效果明显优于其他各组。结论桧木醇/纳米氧化锌/聚己内酯/聚乙二醇纳米纤维型创伤敷料符合目前对于理想型创伤敷料的要求,该新型敷料将来应用于临床治疗耐甲氧西林金黄色葡萄球菌引起的伤口感染,可以减轻伤口部位的炎症反应,具备一定的开发前景。

ObjectiveTo prepare composite nanofibers fabricated using betathujaplicin, zinc oxide nanoparticles, polycaprolactone, and polyethylene glycol （β-T/ZnONPs/PCL/PEG） and evaluate its effect in promoting healing of wounds infected by methicillin-resistant Staphylococcus aureus （MRSA）. MethodsThe composite nanofibers with different formulations were fabricated using electrospinning technique and its structures were observed with scanning electron microscopy. The structure and the chemical bonds of the nanofibers were characterized by Fourier transform infrared spectrometry, and its thermodynamic property was characterized by differential scanning calorimetry. Dilution method was used to evaluate the antibacterial activity, and MTT assay was used to assess the cytotoxicity of the nanofibers. The effect of the nanofibers in promoting wound healing was evaluated in a BALB/c rat model of wound infection by MRSA. ResultsWith diameter of （255.98±56.08） nm, 1%β-T/0.25%ZnONPs/PCL/PEG nanofibers showed a good compatibility between the drug and the carrier material. 0.5%β-T/0.5%ZnONPs/PCL/PEG and 1%β-T/0.25%ZnONPs/PCL/PEG nanofibers had similar antibacterial （P〉0.05） and biocompatibility profiles （P〉0.05）, and both met the GB/T 16886.5-2011 standards. Animal studies showed that all the drug-loaded nanofibers obviously promoted healing of the wounds infected by MRSA on days 7, 11 and 15 following model establishment （P〈0.05）, and dressing with β-T/ZnONPs/PCL/PEG nanofibers achieved a significantly higher wound healing rate than with the other materials on day 11 （P〈0.05）. HE staining also showed that βT/ZnONPs/PCL/PEG nanofibers significantly accelerated wound healing as compared with the other materials. Conclusion β-T/ZnONPs/PCL/PEG nanofibers prepared using electrospinning technique meet the requirements for an ideal wound dressing material and can be a promising material for clinical treatment of wound with MRSA infection.