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妥布霉素增强小直径血管移植物用于局部抗生素递送:初步配方研究。

Tobramycin Supplemented Small-Diameter Vascular Grafts for Local Antibiotic Delivery: A Preliminary Formulation Study.

机构信息

Department of Drug Sciences, Pharmaceutical Section, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy.

Department of Drug Sciences, Pharmacological Section, University of Pavia, Via Taramelli 16, 27100 Pavia, Italy.

出版信息

Int J Mol Sci. 2021 Dec 17;22(24):13557. doi: 10.3390/ijms222413557.

DOI:10.3390/ijms222413557
PMID:34948352
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8709041/
Abstract

Peripheral artery occlusive disease is an emerging cardiovascular disease characterized by the blockage of blood vessels in the limbs and is associated with dysfunction, gangrene, amputation, and a high mortality risk. Possible treatments involve by-pass surgery using autologous vessel grafts, because of the lack of suitable synthetic small-diameter vascular prosthesis. One to five percent of patients experience vascular graft infection, with a high risk of haemorrhage, spreading of the infection, amputation and even death. In this work, an infection-proof vascular graft prototype was designed and manufactured by electrospinning 12.5% / poly-L-lactic-co-glycolic acid solution in 75% / dichloromethane, 23.8% / dimethylformamide and 1.2% / water, loaded with 0.2% /. Polymer and tobramycin concentrations were selected after viscosity and surface tension and after HPLC-UV encapsulation efficiency (EE%) evaluation, respectively. The final drug-loaded prototype had an EE% of 95.58% ± 3.14%, with smooth fibres in the nanometer range and good porosity; graft wall thickness was 291 ± 20.82 μm and its internal diameter was 2.61 ± 0.05 mm. The graft's antimicrobic activity evaluation through time-kill assays demonstrated a significant and strong antibacterial activity over 5 days against and . An indirect cell viability assay on Normal Human Dermal Fibroblasts (NHDF) confirmed the cytocompatibility of the grafts.

摘要

外周动脉闭塞性疾病是一种新兴的心血管疾病,其特征是四肢血管阻塞,并与功能障碍、坏疽、截肢和高死亡率相关。可能的治疗方法包括使用自体血管移植物进行旁路手术,因为缺乏合适的合成小直径血管假体。1%到 5%的患者会出现血管移植物感染,有出血、感染扩散、截肢甚至死亡的高风险。在这项工作中,通过静电纺丝 12.5%/聚(L-丙交酯-co-乙交酯)在 75%/二氯甲烷、23.8%/二甲基甲酰胺和 1.2%/水中的溶液,设计并制造了一种抗感染血管移植物原型,其中载有 0.2%/的聚合物和妥布霉素。聚合物和妥布霉素的浓度分别通过粘度和表面张力以及高效液相色谱-紫外(HPLC-UV)封装效率(EE%)评估后选择。最终的载药原型的 EE%为 95.58%±3.14%,具有纳米级的光滑纤维和良好的孔隙率;移植物壁厚度为 291±20.82μm,内径为 2.61±0.05mm。通过时间杀伤试验评估移植物的抗菌活性表明,在 5 天内对 和 具有显著且强大的抗菌活性。对正常人皮肤成纤维细胞(NHDF)的间接细胞活力测定证实了移植物的细胞相容性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7963/8709041/b6122f8318b6/ijms-22-13557-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7963/8709041/d1735506b02c/ijms-22-13557-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7963/8709041/fc6f696d8cb1/ijms-22-13557-g003.jpg
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