Sebe Istvan, Ostorhazi Eszter, Fekete Aron, Kovacs Krisztian N, Zelko Romana, Kovalszky Ilona, Li Wenyi, Wade John D, Szabo Dora, Otvos Laszlo
University Pharmacy Department of Pharmacy Administration, Semmelweis University, Hogyes Endre Street 7-9, Budapest, 1092, Hungary.
Institute of Medical Microbiology, Semmelweis University, Nagyvarad ter 4, Budapest, 1089, Hungary.
Amino Acids. 2016 Jan;48(1):203-11. doi: 10.1007/s00726-015-2080-4. Epub 2015 Aug 29.
Native and designer cationic antimicrobial peptides are increasingly acknowledged as host defense molecules rather than true antimicrobials. Due to their ability to activate the innate immune system, these structures are used to treat uninfected and bacterially-infected wounds, including those harboring Acinetobacter baumannii. Previously we documented that when administered intramuscularly or topically in liquid formulations, the proline-rich host defense peptide dimer A3-APO accelerates uninfected wound re-epithelization and eliminates systemic and local A. baumannii, methicillin-resistant Staphylococcus aureus and other pathogen load from infected lesions better than conventional antibiotics. In the current study we sought to produce and characterize a novel delivery system, suitable for immediate and convenient application in non-hospital environments. The APO monomer was incorporated into polyvinyl alcohol nanofibers and the complex was polymerized into a solid patch dressing. Mice were subjected to skin abrasion where the wounds were either left uninfected or were inoculated with a near lethal dose of multidrug resistant A. baumannii strain. Analyzed after 3 days, APO monomer-containing patches improved wound appearance significantly better than polymer patches without antibiotics. When compared to colistin, the APO patches accelerated wound healing, and statistically significantly reduced wound size and wound bacterial load. The in vivo antimicrobial effect was more extensive than after intramuscular administration of the peptide drug, by using only one tenth of the active pharmaceutical ingredient. These data suggest that the APO monomer-impregnated nanofiber dressing can be developed as an economical first-line treatment option to skin injuries in general and battlefield burn and blast injuries in particular.
天然和设计的阳离子抗菌肽越来越被认为是宿主防御分子，而非真正的抗菌剂。由于它们能够激活先天免疫系统，这些结构被用于治疗未感染和细菌感染的伤口，包括那些感染鲍曼不动杆菌的伤口。此前我们记录到，当以液体制剂进行肌肉注射或局部给药时，富含脯氨酸的宿主防御肽二聚体A3-APO比传统抗生素能更好地加速未感染伤口的重新上皮化，并消除感染病灶中的全身和局部鲍曼不动杆菌、耐甲氧西林金黄色葡萄球菌及其他病原体负荷。在本研究中，我们试图制备并表征一种新型给药系统，适用于在非医院环境中即时且方便地应用。将APO单体掺入聚乙烯醇纳米纤维中，并将该复合物聚合成固体贴片敷料。对小鼠进行皮肤擦伤处理，伤口要么不感染，要么接种接近致死剂量的多重耐药鲍曼不动杆菌菌株。3天后分析发现，含APO单体的贴片在改善伤口外观方面明显优于不含抗生素的聚合物贴片。与黏菌素相比，APO贴片加速了伤口愈合，并在统计学上显著减小了伤口大小和伤口细菌负荷。通过仅使用十分之一的活性药物成分，体内抗菌效果比肌肉注射肽药物后更广泛。这些数据表明，浸渍有APO单体的纳米纤维敷料可被开发为一种经济的一线治疗选择，用于一般的皮肤损伤，特别是战场烧伤和爆炸伤。
