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负载庆大霉素的脂质体固定化壳聚糖纳米纤维网的抗菌活性

Antibacterial activity of chitosan nanofiber meshes with liposomes immobilized releasing gentamicin.

作者信息

Monteiro Nelson, Martins Margarida, Martins Albino, Fonseca Nuno A, Moreira João N, Reis Rui L, Neves Nuno M

机构信息

3B's Research Group - Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra S. Cláudio do Barco, 4806-909 Caldas das Taipas, Guimarães, Portugal; ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal.

3B's Research Group - Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra S. Cláudio do Barco, 4806-909 Caldas das Taipas, Guimarães, Portugal; ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal; IBB-Institute for Biotechnology and Bioengineering, Centre of Biological Engineering, University of Minho, Campus de Gualtar, Braga, Portugal.

出版信息

Acta Biomater. 2015 May;18:196-205. doi: 10.1016/j.actbio.2015.02.018. Epub 2015 Mar 5.

DOI:10.1016/j.actbio.2015.02.018
PMID:25749293
Abstract

Chitsan (Ch) nanofiber mesh (NFM) is a material with natural characteristics favoring its use in human wound dressing. The present work proposes a gentamicin-loaded liposome immobilized at the surface of Ch NFMs to promote its antibacterial activity. To achieve this purpose, Ch NFMs were functionalized with thiol groups, and gentamicin-loaded liposomes were covalently immobilized by the reaction of the SH groups with maleimide. The maximum concentration of SH groups (55.52±11.19nmolcm(-2)) was obtained at pH 7. A fluorescent dye was covalently bound to the SH groups present at the surface of electrospun Ch NFMs. Their spatial distribution was uniform throughout the NFMs when analyzed by fluorescence microscopy. Gentamicin was successfully encapsulated into the liposomes with an efficiency of 17%. Gentamicin-loaded liposomes were uniformly distributed at the surface of the Ch NFMs and the drug release kinetic showed a sustained release of gentamicin during 16h, achieving a steady state at 24h. The in vitro susceptibility tests confirmed that the gentamicin released from the liposomes immobilized at the surface of electrospun Ch NFM has bactericidal activity against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. The results show that the developed system has promising performance for wound dressing applications, avoiding infections caused by these common pathogens.

摘要

壳聚糖(Ch)纳米纤维网(NFM)是一种具有天然特性的材料,有利于其在人类伤口敷料中的应用。本研究提出将负载庆大霉素的脂质体固定在Ch NFM表面,以提高其抗菌活性。为实现这一目的,对Ch NFM进行硫醇基功能化,通过SH基团与马来酰亚胺的反应将负载庆大霉素的脂质体共价固定。在pH 7时获得了最大浓度的SH基团(55.52±11.19nmolcm(-2))。将一种荧光染料共价结合到电纺Ch NFM表面存在的SH基团上。通过荧光显微镜分析时,它们在整个NFM中的空间分布是均匀的。庆大霉素成功包封到脂质体中,包封效率为17%。负载庆大霉素的脂质体均匀分布在Ch NFM表面,药物释放动力学显示庆大霉素在16小时内持续释放,在24小时达到稳态。体外药敏试验证实,从固定在电纺Ch NFM表面的脂质体中释放的庆大霉素对大肠杆菌、铜绿假单胞菌和金黄色葡萄球菌具有杀菌活性。结果表明,所开发的系统在伤口敷料应用中具有良好的性能,可避免由这些常见病原体引起的感染。

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