Dual delivery of active antibactericidal agents and bone morphogenetic protein at sustainable high concentrations using biodegradable sheath-core-structured drug-eluting nanofibers

使用可生物降解的鞘芯结构药物洗脱纳米纤维以可持续的高浓度双重输送活性抗菌剂和骨形态发生蛋白

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作者:Yung-Hen Hsu, Chang-Tun Lin, Yi-Hsun Yu, Ying-Chao Chou, Shih-Jung Liu, Err-Cheng Chan

Abstract

In this study, we developed biodegradable sheath-core-structured drug-eluting nanofibers for sustainable delivery of antibiotics (vancomycin and ceftazidime) and recombinant human bone morphogenetic protein (rhBMP-2) via electrospinning. To prepare the biodegradable sheath-core nanofibers, we first prepared solutions of poly(d,l)-lactide-co-glycolide, vancomycin, and ceftazidime in 1,1,1,3,3,3-hexafluoro-2-propanol and rhBMP-2 in phosphate-buffered solution. The poly(d,l)-lactide-co-glycolide/antibiotics and rhBMP-2 solutions were then fed into two different capillary tubes controlled by two independent pumps for coaxial electrospinning. The electrospun nanofiber morphology was observed under a scanning electron microscope. We further characterized the in vitro antibiotic release from the nanofibers via high-performance liquid chromatography and that of rhBMP-2 via enzyme-linked immunosorbent assay and alkaline phosphatase activity. We showed that the biodegradable coaxially electrospun nanofibers could release high vancomycin/ceftazidime concentrations (well above the minimum inhibition concentration [MIC]90) and rhBMP-2 for >4 weeks. These experimental results demonstrate that novel biodegradable nanofibers can be constructed with various pharmaceuticals and proteins for long-term drug deliveries.

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