负载抗菌多肽温敏水凝胶的制备及性能研究

Preparation and properties of antimicrobial peptide-loaded thermosensitive hydrogel

目的:构建透明质酸(hyaluronic acid,HA)/羟丙基甲基纤维素(hydroxypropyl methylcellulose,HPMC)/甘油温敏水凝胶体系并搭载抗菌多肽芬母多肽(Funme peptide,FP),检测水凝胶的相关理化性质、抗菌性能以及对小鼠皮肤创伤愈合的促进作用。方法:采用物理交联的方法制备HA/HPMC/甘油-FP温敏水凝胶,分析HA和甘油的含量对凝胶化温度(gelation temperature,T_(gel))的影响。利用流变学检测、傅里叶变换红外光谱仪以及扫描电子显微镜对制备的水凝胶进行理化性能表征。同时对水凝胶的生物相容性和抗菌性进行观察研究。构建小鼠背部直径10 mm的全层皮肤缺损感染创面模型,在注射水凝胶后,于第5、10、15天观察创面愈合情况,计算创面愈合率。结果:在HA、HPMC和甘油的比例为2∶7∶20时,水凝胶具有理想的T_(gel);水凝胶内部呈孔隙率高、孔径较均匀的三维结构,各成分间未发生化学反应,同时该水凝胶具有良好的生物相容性,对大肠杆菌(Escherichia coli,E.coli)具有显著的抗菌效果。动物实验表明,HA/HPMC/甘油-FP水凝胶处理的小鼠背部创面愈合明显优于对照组。结论:该温敏水凝胶在医用创伤敷料领域具有良好的应用前景。

Objective:Preparation and characterization of a thermo-sensitive hydrogel consisting of hyaluronic acid(HA),hydroxypropyl methylcellulose(HPMC)and glycerol,and loaded with antimicrobial peptide Funme(FP).Methods:HA/HPMC/Glycerol-FP hydrogels were synthesized by physical cross-linking,and the thermosensitive behavior of the hydrogels was analyzed.The physicochemical properties of the hydrogels were characterized by rheological test,Fourier transform infrared spectroscopy(FTIR)and scanning electron microscope(SEM).The biocompatibility and antibacterial activities were also investigated in vitro.A full-thickness skin defect model with a diameter of 10 mm was constructed on the back of the mouse and the wound healing rate was recorded after treatment with hydrogel.Results:HA/HPMC/Glycerol-FP hydrogel exhibited desirable gel temperature when the ratio of HA,HPMC and glycerol was 2∶7∶20 and no chemical reactions occurred during hydrogelation.Moreover,the hydrogel exhibited good biocompatibility on L929 cells and showed a significant inhibitory effect on Escherichia coli(E.coli).Animal experiments showed that wound healing in the HA/HPMC/Glycerol-FP group was significantly better than the control group.Conclusion:HA/HPMC/Glycerol-FP is a conductive material that has great application prospects in bio-medical dressings.