Abstract：
OBJECTIVE: Previously, we developed a novel double-coated sinus stent containing ciprofloxacin (inner layer) and azithromycin (outer layer) (CASS), but released drug concentrations were found to be insufficient for clinical usage. Our objectives are to improve drug release of CASS and assess safety and pharmacokinetics in rabbits.
METHODS: Dip coating was used to create the CASS with 2 mg ciprofloxacin and 5 mg azithromycin. A uniformed double coating was assessed with scanning electron microscopy (SEM), and the release patterns of both drugs and lactate dehydrogenase (LDH) assay were evaluated over 14 days in vitro. Safety, tolerability, and pharmacokinetics of the CASS were tested in rabbits through insertion into the maxillary sinus and evaluated with nasal endoscopy, CT scans, histology, blood counts and chemistries, and in vivo drug release.
RESULTS: SEM confirmed the uniformity of the dual coating of ciprofloxacin and azithromycin, and thickness (μm) was found to be 14.7 ± 2.4 and 28.1 ± 4.6, respectively. The inner coated ciprofloxacin showed a sustained release over 14 days (release %) when soaked in saline solution (day 7, 86.2 ± 3.4 vs. day 14,99.2 ± 5.1). In vivo analysis showed that after 12 days, 78.92 ± 7.67% of CP and 84.12 ± 0.45% of AZ were released into the sinus. There were no significant differences in body weight, white blood cell counts, and radiographic changes before and after CASS placement. No significant histological changes were observed compared to the contralateral control side.
CONCLUSIONS: Findings suggest that the CASS is an effective method for delivering therapeutic levels of antibiotics. Further studies are needed to validate efficacy in a preclinical sinusitis model.
METHODS: N/A Laryngoscope, 2024.
METHODS: Dip coating was used to create the CASS with 2 mg ciprofloxacin and 5 mg azithromycin. A uniformed double coating was assessed with scanning electron microscopy (SEM), and the release patterns of both drugs and lactate dehydrogenase (LDH) assay were evaluated over 14 days in vitro. Safety, tolerability, and pharmacokinetics of the CASS were tested in rabbits through insertion into the maxillary sinus and evaluated with nasal endoscopy, CT scans, histology, blood counts and chemistries, and in vivo drug release.
RESULTS: SEM confirmed the uniformity of the dual coating of ciprofloxacin and azithromycin, and thickness (μm) was found to be 14.7 ± 2.4 and 28.1 ± 4.6, respectively. The inner coated ciprofloxacin showed a sustained release over 14 days (release %) when soaked in saline solution (day 7, 86.2 ± 3.4 vs. day 14,99.2 ± 5.1). In vivo analysis showed that after 12 days, 78.92 ± 7.67% of CP and 84.12 ± 0.45% of AZ were released into the sinus. There were no significant differences in body weight, white blood cell counts, and radiographic changes before and after CASS placement. No significant histological changes were observed compared to the contralateral control side.
CONCLUSIONS: Findings suggest that the CASS is an effective method for delivering therapeutic levels of antibiotics. Further studies are needed to validate efficacy in a preclinical sinusitis model.
METHODS: N/A Laryngoscope, 2024.
摘要：
目标：以前，我们开发了一种包含环丙沙星（内层）和阿奇霉素（外层）（CASS）的新型双涂层鼻窦支架，但是发现释放的药物浓度不足以用于临床使用。我们的目标是改善CASS的药物释放并评估兔体内的安全性和药代动力学。
方法：浸渍包衣用于产生含有2mg环丙沙星和5mg阿奇霉素的CASS。用扫描电子显微镜（SEM）评估均匀的双涂层，并在体外14天内评估了两种药物和乳酸脱氢酶（LDH）测定的释放模式。安全,耐受性,CASS的药代动力学在兔中通过插入上颌窦进行测试，并通过鼻内窥镜检查进行评估，CT扫描,组织学,血细胞计数和化学物质，和体内药物释放。
结果：SEM证实了环丙沙星和阿奇霉素双重涂层的均匀性，和厚度（μm）分别为14.7±2.4和28.1±4.6。当浸泡在盐溶液中时，内涂层环丙沙星显示出持续释放超过14天（释放％）（第7天，86.2±3.4vs.第14,99.2±5.1天）。体内分析显示，12天后，78.92±7.67%的CP和84.12±0.45%的AZ释放到窦中。体重没有显着差异，白细胞计数,以及CASS放置前后的射线照相变化。与对侧对照侧相比，未观察到明显的组织学变化。
结论：研究结果表明，CASS是提供治疗水平抗生素的有效方法。需要进一步的研究来验证临床前鼻窦炎模型的功效。
方法：N/A喉镜，2024.
方法：浸渍包衣用于产生含有2mg环丙沙星和5mg阿奇霉素的CASS。用扫描电子显微镜（SEM）评估均匀的双涂层，并在体外14天内评估了两种药物和乳酸脱氢酶（LDH）测定的释放模式。安全,耐受性,CASS的药代动力学在兔中通过插入上颌窦进行测试，并通过鼻内窥镜检查进行评估，CT扫描,组织学,血细胞计数和化学物质，和体内药物释放。
结果：SEM证实了环丙沙星和阿奇霉素双重涂层的均匀性，和厚度（μm）分别为14.7±2.4和28.1±4.6。当浸泡在盐溶液中时，内涂层环丙沙星显示出持续释放超过14天（释放％）（第7天，86.2±3.4vs.第14,99.2±5.1天）。体内分析显示，12天后，78.92±7.67%的CP和84.12±0.45%的AZ释放到窦中。体重没有显着差异，白细胞计数,以及CASS放置前后的射线照相变化。与对侧对照侧相比，未观察到明显的组织学变化。
结论：研究结果表明，CASS是提供治疗水平抗生素的有效方法。需要进一步的研究来验证临床前鼻窦炎模型的功效。
方法：N/A喉镜，2024.
