Efficacy and safety profile of the novel antimicrobial peptide PXL150 in a mouse model of infected burn wounds
Efficacy and safety profile of the novel antimicrobial peptide PXL150 in a mouse model of infected burn wounds
复制标题
DOI：
10.1016/j.ijantimicag.2014.12.015
复制
发表时间：
2015-05-01
影响因子：
10.8
通讯作者：
Hakansson, Joakim
中科院分区：
文献类型：
--
作者：
Bjorn, Camilla;Noppa, Laila;Hakansson, Joakim
开发新型抗菌疗法的迫切需要激发了人们对抗菌肽作为治疗传染病的候选药物的兴趣。本研究的目的是评估羟丙基纤维素 (HPC) 凝胶中配制的合成抗菌肽 PXL150 对铜绿假单胞菌的体外和感染烧伤创面小鼠体内模型的抗感染作用，并评估 PXL150 在大鼠和兔子中的体内安全性。最小杀菌浓度分析表明，PXL150 在体外对铜绿假单胞菌具有显着的功效，在 HPC 凝胶中配制肽时，这种功效得到了进一步增强。与未经治疗或安慰剂治疗的对照相比，连续四天每天两次使用 HPC 凝胶中的 1.25、2.5、5、10 和 20 mg/g PXL150 显着减少了烧伤创面的细菌计数。对细菌的连续生物发光测量表明，PXL150 在感染后第一天，浓度 >= 2.5 mg/g 时就已经具有明显的抗感染作用。在非临床安全性研究中，PXL150分别对大鼠和兔子进行全身和局部重复给药后显示出良好的安全性。总之，这些数据支持 PXL150 有潜力成为治疗感染烧伤创面的有效且安全的候选药物。这些发现鼓励 PXL150 作为微生物感染的新型局部治疗药物的发展。 (C) 2015 Elsevier B.V. 和国际化疗协会。版权所有。
The urgent need to develop novel antimicrobial therapies has stimulated interest in antimicrobial peptides as therapeutic candidates for the treatment of infectious diseases. The aim of this study was to evaluate the anti-infectious effect of the synthetic antimicrobial peptide PXL150, formulated in hydroxypropyl cellulose (HPC) gel, on Pseudomonas aeruginosa in vitro and in an in vivo mouse model of infected burn wounds as well as to assess the in vivo safety profile of PXL150 in rats and rabbits. Minimal microbicidal concentration analysis showed prominent efficacy of PXL150 against P. aeruginosa in vitro, which was further enhanced in formulating the peptide in HPC gel. Application of 1.25, 2.5, 5, 10 and 20 mg/g PXL150 in HPC gel twice daily for four consecutive days significantly reduced bacterial counts in the burn wounds compared with non-treated or placebo-treated controls. Continuous bioluminescence measurements of the bacteria revealed a pronounced anti-infective effect already at the first day post infection by PXL150 in concentrations of >= 2.5 mg/g. In the non-clinical safety studies, PXL150 showed a favourable safety profile following repeated administration systemically and locally in rats and rabbits, respectively. In conclusion, these data support that PXL150 has the potential to be an effective and safe drug candidate for the treatment of infected burn wounds. The findings encourage the progression of PXL150 as a novel topical treatment of microbial infections. (C) 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.