Zhu Chongyu, Zhao Jinxin, Kempe Kristian, Wilson Paul, Wang Jiping, Velkov Tony, Li Jian, Davis Thomas P, Whittaker Michael R, Haddleton David M
Department of Chemistry, University of Warwick, CV4 7AL, Coventry, UK.
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
Macromol Biosci. 2017 Feb;17(2). doi: 10.1002/mabi.201600320. Epub 2016 Sep 13.
There is an urgent unmet medical need for new treatments for wound and burn infections caused by multidrug-resistant Gram-negative "superbugs," especially the problematic Pseudomonas aeruginosa. In this work, the incorporation of colistin, a potent lipopeptide into a self-healable hydrogel (via dynamic imine bond formation) following the chemical reaction between the amine groups present in glycol chitosan and an aldehyde-modified poly(ethylene glycol), is reported. The storage module (G') of the colistin-loaded hydrogel ranges from 1.3 to 5.3 kPa by varying the amount of the cross-linker and colistin loading providing different options for topical wound healing. The majority of the colistin is released from the hydrogel within 24 h and remains active as demonstrated by both antibacterial in vitro disk diffusion and time-kill assays. Moreover and pleasingly, the colistin-loaded hydrogel performs almost equally well as native colistin against both the colistin-sensitive and also colistin-resistant P. aeruginosa strain in the in vivo animal "burn" infection model despite exhibiting a slower killing profile in vitro. Based on this antibiotic performance along with the biodegradability of the product, it is believed the colistin-loaded hydrogel to be a potential localized wound-healing formulation to treat burn wounds against microbial infection.
对于由多重耐药革兰氏阴性“超级细菌”引起的伤口和烧伤感染，尤其是问题重重的铜绿假单胞菌，目前迫切需要新的治疗方法。在这项工作中，报告了通过壳聚糖二醇中存在的胺基与醛修饰的聚乙二醇之间的化学反应，将强效脂肽多粘菌素掺入可自愈水凝胶（通过动态亚胺键形成）的过程。通过改变交联剂的量和多粘菌素负载量，负载多粘菌素的水凝胶的储能模量（G'）在1.3至5.3 kPa范围内，为局部伤口愈合提供了不同选择。大部分多粘菌素在24小时内从水凝胶中释放出来，并保持活性，体外抗菌纸片扩散试验和时间杀菌试验均证明了这一点。此外，令人欣慰的是，在体内动物“烧伤”感染模型中，负载多粘菌素的水凝胶对多粘菌素敏感和耐药的铜绿假单胞菌菌株的表现几乎与天然多粘菌素一样好，尽管在体外显示出较慢的杀菌曲线。基于这种抗生素性能以及产品的生物降解性，人们认为负载多粘菌素的水凝胶是一种潜在的局部伤口愈合制剂，可用于治疗烧伤伤口的微生物感染。
