Repurposing old antibiotics into more effective and safer formulations is an emergent approach to tackle the growing threat of antimicrobial resistance. Herein, a peptide hydrogel is reported for the localized and sustained release of polymyxin B (PMB), a decade-old antibiotic with increasing clinical utility for treating multidrug-resistant Gram-negative bacterial infections. The hydrogel is assembled by additing PMB solution into a rationally designed peptide amphiphile (PA) solution and its mechanical properties can be adjusted through the addition of counterions, envisioning its application in diverse infection scenarios. Sustained release of PMB from the hydrogel over a 5-day period and prolonged antimicrobial activities against Gram-negative bacteria are observed. The localized release of active PMB from the hydrogel is shown to be effective in vivo for treating Pseudomonas aeruginosa infection in the Galleria mellonella burn wound infection model, dramatically reducing the mortality from 93% to 13%. Complementary antimicrobial activity against Gram-positive Staphylococcus aureus and enhanced antimicrobial effect against the Gram-negative Acinetobacter baumannii are observed when an additional antibiotic fusidic acid is incorporated into the hydrogen network. These results demonstrate the potential of the PMB-triggered PA hydrogel as a versatile platform for the localized and sustained delivery of combined antimicrobial therapies.

中文翻译：

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多粘菌素 B 触发的肽水凝胶组装用于联合抗菌治疗的局部和持续释放

将旧抗生素重新用于更有效和更安全的配方是应对日益严重的抗菌素耐药性威胁的新兴方法。本文报道了一种多肽水凝胶，用于局部和持续释放多粘菌素 B (PMB)，这是一种已有十年历史的抗生素，在治疗多药耐药革兰氏阴性细菌感染方面具有越来越多的临床效用。通过将 PMB 溶液添加到合理设计的肽两亲物 (PA) 溶液中来组装水凝胶，并且可以通过添加抗衡离子来调整其机械性能，设想其在各种感染场景中的应用。观察到 PMB 从水凝胶中持续释放 5 天，并观察到对革兰氏阴性菌的抗菌活性延长。大肠菌群烧伤创面感染模型中的铜绿假单胞菌感染，将死亡率从 93% 大幅降低至 13%。当将额外的抗生素夫西地酸掺入氢网络时，观察到对革兰氏阳性金黄色葡萄球菌的补充抗菌活性和对革兰氏阴性鲍曼不动杆菌的增强抗菌作用。这些结果证明了 PMB 触发的 PA 水凝胶作为一个多功能平台的潜力，可用于局部和持续交付联合抗菌疗法。