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

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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.

Clinical Relevance:

In this study, we developed and fabricated hybrid biodegradable, antibiotic-eluting, nanofiber-loaded endovascular prostheses by using the electrospinning technique for local and sustained drug delivery to the aortic aneurysm. These experimental results showed that the biodegradable vancomycin-eluting nanofibers are biocompatible, significantly contribute to the achievement of sustainable delivery of high-dose antibiotics to the aneurysm sac and the adjacent aortic wall, and may increase the successful rate of using endovascular treatment for mycotic aortic aneurysm in the clinical application.

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