Poly(lactide-co-glycolide) Nanoparticles for Prolonged Therapeutic Efficacy of Esculentin-1a-Derived Antimicrobial Peptides against Pseudomonas aeruginosa Lung Infection: in Vitro and in Vivo Studies
Poly(lactide-co-glycolide) Nanoparticles for Prolonged Therapeutic Efficacy of Esculentin-1a-Derived Antimicrobial Peptides against Pseudomonas aeruginosa Lung Infection: in Vitro and in Vivo Studies
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DOI：
10.1021/acs.biomac.8b01829
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发表时间：
2019-05-01
影响因子：
6.2
通讯作者：
Mangoni, Maria Luisa
中科院分区：
文献类型：
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作者：
Casciaro, Bruno;d'Angelo, Ivana;Mangoni, Maria Luisa
由于其良好的体外抗多药耐药活性，抗菌肽(AMPs)有望治疗囊性纤维化(CF)患者的铜绿假单胞菌肺部感染。在这项工作中，我们成功地将聚丙交酯-乙交酯(PLGA)纳米粒应用于从蛙皮提取物中提取的AMP，即ESC(1-21)和ESC(1-21)-1c(ESC多肽)。通过人工CF粘液和模拟细菌细胞外基质，在体外实现了多肽的转运。这些制剂是通过患者已经可用的液体喷雾器有效地输送的。值得注意的是，ESC多肽纳米颗粒在体外和体内长期抑制铜绿假单胞菌生长方面显示出更好的效果。在铜绿假单胞菌肺部感染的小鼠模型中，一次气管内注射ESC多肽纳米颗粒可使肺部细菌负荷减少3对数，最长可达36小时。总体而言，结果揭示了PLGA纳米颗粒作为AMPs可靠的肺部递送系统的潜力。
Due to their excellent in vitro activity against multidrug resistant bacteria, antimicrobial peptides (AMPs) hold promise for treatment of Pseudomonas aeruginosa lung infections in cystic fibrosis (CF) sufferers. In this work, poly(lactide-co-glycolide) (PLGA) nanoparticles for lung delivery of AMPs deriving from the frog-skin esculentin-la, namely, Esc(1-21) and Esc(1-21)-1c (Esc peptides), were successfully developed. Improved peptide transport through artificial CF mucus and simulated bacterial extracellular matrix was achieved in vitro. The formulations were effectively delivered through a liquid jet nebulizer already available to patients. Notably, Esc peptide-loaded nanoparticles displayed an improved efficacy in inhibiting P. aeruginosa growth in vitro and in vivo in the long term. A single intratracheal administration of Esc peptide-loaded nanoparticles in a mouse model of P. aeruginosa lung infection resulted in a 3-log reduction of pulmonary bacterial burden up to 36 h. Overall, results unravel the potential of PLGA nanoparticles as a reliable delivery system of AMPs to lungs.