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体外评价左氧氟沙星和阿奇霉素鼻窦支架对铜绿假单胞菌生物膜的作用。

In-vitro evaluation of a ciprofloxacin and azithromycin sinus stent for Pseudomonas aeruginosa biofilms.

机构信息

Department of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL.

Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL.

出版信息

Int Forum Allergy Rhinol. 2020 Jan;10(1):121-127. doi: 10.1002/alr.22475. Epub 2019 Nov 6.

Abstract

BACKGROUND

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease characterized by persistent inflammation and bacterial infection. Ciprofloxacin and azithromycin are commonly prescribed antibiotics for CRS, but the ability to provide targeted release in the sinuses could mitigate side effects and improve drug concentrations at the infected site. This study was aimed to evaluate the efficacy of the novel ciprofloxacin-azithromycin sinus stent (CASS) in vitro.

METHODS

The CASS was created by coating ciprofloxacin (hydrophilic, inner layer) and azithromycin (hydrophobic, outer layer) onto a biodegradable poly-l-lactic acid (PLLA) stent. In-vitro evaluation included: (1) assessment of drug-coating stability within the stent using scanning electron microscopy (SEM); (2) determination of ciprofloxacin and azithromycin release kinetics; and (3) assessment of anti-biofilm activities against Pseudomonas aeruginosa.

RESULTS

The ciprofloxacin nanoparticle suspension in the inner layer was confirmed by zeta potential. Both ciprofloxacin (60 µg) and azithromycin (3 mg) were uniformly coated on the surface of the PLLA stents. The CASS showed ciprofloxacin/azithromycin sustained release patterns, with 80.55 ± 11.61% of ciprofloxacin and 93.85 ± 6.9% of azithromycin released by 28 days. The CASS also significantly reduced P aeruginosa biofilm mass compared with bare stents and controls (relative optical density units at 590-nm optical density: CASS, 0.037 ± 0.006; bare stent, 0.911 ± 0.015; control, 1.000 ± 0.000; p < 0.001; n = 3).

CONCLUSION

The CASS maintains a uniform coating and sustained delivery of ciprofloxacin and azithromycin, providing anti-biofilm activities against P aeruginosa. Further studies evaluating the efficacy of CASS in a preclinical model are planned.

摘要

背景

慢性鼻-鼻窦炎(CRS)是一种以持续性炎症和细菌感染为特征的慢性炎症性疾病。环丙沙星和阿奇霉素是治疗 CRS 的常用抗生素,但能够在鼻窦中提供靶向释放,可以减轻副作用并提高感染部位的药物浓度。本研究旨在评估新型环丙沙星-阿奇霉素鼻窦支架(CASS)的体外疗效。

方法

CASS 通过将环丙沙星(亲水性,内层)和阿奇霉素(疏水性,外层)涂覆在可生物降解的聚-L-乳酸(PLLA)支架上来制备。体外评估包括:(1)使用扫描电子显微镜(SEM)评估支架内药物涂层的稳定性;(2)测定环丙沙星和阿奇霉素的释放动力学;(3)评估抗铜绿假单胞菌生物膜活性。

结果

通过zeta 电位证实了内层中环丙沙星纳米颗粒悬浮液的存在。环丙沙星(60μg)和阿奇霉素(3mg)均均匀涂覆在 PLLA 支架表面。CASS 显示出环丙沙星/阿奇霉素的持续释放模式,28 天后释放了 80.55±11.61%的环丙沙星和 93.85±6.9%的阿奇霉素。与裸支架和对照相比,CASS 还显著减少了铜绿假单胞菌生物膜的质量(590nm 光密度的相对光密度单位:CASS,0.037±0.006;裸支架,0.911±0.015;对照,1.000±0.000;p<0.001;n=3)。

结论

CASS 保持了环丙沙星和阿奇霉素的均匀涂层和持续释放,提供了针对铜绿假单胞菌的抗生物膜活性。计划进一步研究 CASS 在临床前模型中的疗效。

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