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.