摘要
为解决Temporin-GHaR稳定性差及溶血毒性高的问题,采用制剂设计技术,构建负载Temporin-GHaR的温敏型羧甲基壳聚糖/羟丙基甲基纤维素/泊洛沙姆四元复合水凝胶CMCS/HPMC/P407/P188(CHPP/GHaR)。经响应面法优化配方,制得的水凝胶具多孔纤维网络结构,兼备剪切稀化、自愈合与可注射性,溶胀率良好。结果表明:释放实验显示,CHPP/GHaR突释风险低;生物相容性评价证实,负载200μmol·L^(-1)GHaR的水凝胶溶血率低,且对角质形成细胞与脐静脉血管上皮细胞无明显细胞毒性;体外抗菌实验显示,CHPP/GHaR对耐甲氧西林金黄色葡萄球菌、大肠杆菌和铜绿假单胞菌的抑菌率超99%。研究结果可为耐药菌感染治疗提供新型候选材料。
In order to solve the problems of the poor stability and high hemolytic toxicity of Temporin-GHaR,the preparation design technology was used to construct a thermosensitive quaternary composite hydrogel of carboxymethyl chitosan/hydroxypropyl methylcellulose/poloxamer loaded with Temporin-GHaR(CHPP/GHaR).The response surface method was used to optimize the formulation,and the obtained hydrogel with a porous fiber network structure exhibited shear-thinning,self-healing,and injectability,with a swelling rate of 161.5%.The release experiments tests showed a sustained release of 55%within 40 hours with low burst release risk.Biocompatibility evaluation test confirmed that the hydrogel loaded with 200μmol·L^(-1) GHaR had only 2.2%hemolysis rate and no significant cytotoxicity to keratinocytes and umbilical vein endothelial cells.In vitro antimicrobial experiments demonstrated that CHPP/GHaR achieved above 99%inhibition rates against methicillin-resistant Staphylococcus aureus,Escherichia coli,and Pseudomonas aeruginosa.Our findings provide a new candidate material for the treatment of the drug-resistant bacterialinfections.
作者
邓文欢
胡芳
薛治巨
周巾琪
张英霞
DENG Wenhuan;HU Fang;XUE Zhiju;ZHOU Jinqi;ZHANG Yingxia(School of Pharmaceutical Sciences,Hainan University,Haikou 570228,China;Key Laboratory of Tropical Biological Resources of Ministry of Education,Hainan University,Haikou 570228,China)
基金
国家自然科学基金项目(32560221)
海南省重点研发计划项目(ZDYF2025SHFZ033)
海南省东方市国家现代农业产业园项目(3.1)。
