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一种新型载抗生素可生物降解纳米纤维复合血管内移植物持续局部递增高浓度万古霉素治疗感染性主动脉瘤

Sustained local delivery of high-concentration vancomycin from a hybrid biodegradable, antibiotic-eluting, nanofiber-loaded endovascular prosthesis for treatment of mycotic aortic aneurysms.

机构信息

Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan.

Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan.

出版信息

J Vasc Surg. 2018 Aug;68(2):597-606. doi: 10.1016/j.jvs.2017.07.142. Epub 2017 Oct 21.

Abstract

BACKGROUND

Endovascular repair for mycotic aortic aneurysm (MAA) is a less invasive alternative to open surgery, although the placement of a stent graft in an infected environment remains controversial. In this study, we developed hybrid biodegradable, vancomycin-eluting, nanofiber-loaded endovascular prostheses and evaluated antibiotic release from the endovascular prostheses both in vitro and in vivo.

METHODS

Poly(D,L)-lactide-co-glycolide and vancomycin were dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. This solution was electrospun into nanofibrous tubes, which were mounted onto commercial vascular stents and endovascular aortic stent grafts. In vitro antibiotic release from the nanofibers was characterized using an elution method and high-performance liquid chromatography. Antibiotic release from the hybrid stent graft was analyzed in a three-dimensional-printed model of a circulating MAA. The in vivo drug release characteristics were examined by implanting the antibiotic-eluting stents in the abdominal aorta of New Zealand white rabbits (n = 15).

RESULTS

The in vitro study demonstrated that the biodegradable nanofibers and the nanofiber-loaded stent graft provided sustained release of high concentrations of vancomycin for up to 30 days. The in vivo study showed that the nanofiber-loaded stent exhibited excellent biocompatibility and released high concentrations of vancomycin into the local aortic wall for 8 weeks.

CONCLUSIONS

The proposed biodegradable vancomycin-eluting nanofibers significantly contribute to the achievement of local and sustainable delivery of antibiotics to the aneurysm sac and the aortic wall, and these nanofibers may have therapeutic applications for MAAs.

摘要

背景

血管内修复治疗感染性主动脉瘤(MAA)是一种比开放手术更具侵入性的替代方法,尽管在感染环境中放置支架移植物仍然存在争议。在这项研究中,我们开发了混合可生物降解、万古霉素洗脱、负载纳米纤维的血管内假体,并在体外和体内评估了血管内假体的抗生素释放。

方法

将聚(D,L)-丙交酯-共-乙交酯和万古霉素溶解在 1,1,1,3,3,3-六氟-2-丙醇中。该溶液通过静电纺丝制成纳米纤维管,然后将其安装到商业血管支架和血管内主动脉支架移植物上。使用洗脱法和高效液相色谱法对纳米纤维的体外抗生素释放进行了表征。在循环 MAA 的三维打印模型中分析了混合支架移植物的抗生素释放。通过将载药支架植入新西兰白兔的腹主动脉(n=15)来检查体内药物释放特性。

结果

体外研究表明,可生物降解的纳米纤维和负载纳米纤维的支架移植物可在长达 30 天的时间内持续释放高浓度的万古霉素。体内研究表明,负载纳米纤维的支架表现出优异的生物相容性,并在 8 周内将高浓度的万古霉素释放到局部主动脉壁。

结论

提出的可生物降解的万古霉素洗脱纳米纤维显著有助于实现局部和持续输送抗生素到动脉瘤囊和主动脉壁,并且这些纳米纤维可能对 MAA 具有治疗应用。

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