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一种负载Temporin-GHaR肽的CMCS/HPMC/P407/P188复合水凝胶制备及其抗菌作用研究

Preparation of CMCS/HPMC/P407/P188 thermosensitive injectable composite hydrogel with Temporin-GHaR and its antibacterial effect

  • 摘要: 为了解决抗菌肽Temporin-GHaR稳定性差、溶血毒性高的问题,采用制剂设计技术,构建了负载抗菌肽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(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:释放试验显示CHPP@GHaR突释风险低;生物相容性评价证实,负载200 μM 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;体外抗菌实验表明,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%。研究结果为耐药菌感染治疗提供了新型候选材料。

     

    Abstract: Antimicrobial peptides (AMPs) have become a research hotspot in anti-infection studies due to their broad-spectrum antimicrobial activity and low resistance, but their clinical application is limited by poor stability and high hemolytic toxicity. This study constructed a thermosensitive quaternary composite hydrogel of carboxymethyl chitosan/hydroxypropyl methylcellulose/poloxamer loaded with the antimicrobial peptide Temporin-GHaR (CHPP@GHaR). The hydrogel, optimized by response surface methodology, exhibits a porous fiber network structure, shear-thinning, self-healing, and injectability, with a swelling rate of 161.5%. Drug release tests showed a sustained release of 55% within 40 hours with low burst release risk. Biocompatibility evaluation confirmed that the hydrogel loaded with 200 μM 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 over 99% inhibition rates against methicillin-resistant Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, which was more than 10 times higher than the control group. This study preliminarily addresses the stability and toxicity issues of Temporin-GHaR, and CHPP@GHaR, with its high antimicrobial activity and biosafety, provides a new candidate material for the treatment of resistant bacterial infections.

     

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