Controlled delivery of ciprofloxacin and ivacaftor via sinus stent in a preclinical model of Pseudomonas sinusitis
Controlled delivery of ciprofloxacin and ivacaftor via sinus stent in a preclinical model of Pseudomonas sinusitis
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DOI：
10.1002/alr.22514
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发表时间：
2019-12-23
影响因子：
6.4
通讯作者：
Cho, Do-Yeon
中科院分区：
文献类型：
--
作者：
Lim, Dong-Jin;McCormick, Justin;Cho, Do-Yeon
背景铜绿假单胞菌常见于慢性鼻窦炎（CRS），且常对抗生素治疗产生耐药性。我们最近描述了环丙沙星和ivacitor释放生物可降解窦内支架（CISS）？一种局部高浓度给药环丙沙星和粘膜纤毛激活剂（ivacaftor），延长粘膜接触时间和持续给药的给药系统。本研究的目的是评价CISS对铜绿假单胞菌（PAO1株）鼻窦炎兔模型的疗效。方法采用生物可降解聚d / l -乳酸（PLLA）包被双层环丙沙星/ ivvacaftor。在PAO1诱导感染1周后，通过背窦切开术将10个窦内支架（5个裸PLLA支架对照，5个CISSs支架对照）单侧放置在兔上颌窦内。植入支架后3周，通过鼻窦培养、鼻内窥镜、计算机断层扫描、组织病理学和体内鼻窦电位差（SPD）测定对动物进行评估。结果CISS治疗家兔的计算机断层扫描（Kerschner增量评分：对照组，0.55 +/- 0.92；CISS, -5.92 +/- 1.69; p = 0.024）和内窥镜检查（对照组，4.0 +/- 0.0；CISS, 1.875 +/- 0.74; p = 0.003）评分显著降低。观察到PAO1降低了2个对数（对照组，-2.14 +/- 0.77；CISS, 1.84 +/- 1.52; p = 0.047）。SPD显示，与对照组相比，CISS组Cl-转运显著增加（Cl- free + forskolin Delta PD：对照组，-4.23 +/- 1.04 mV； CISS, -18.36 +/- 6.31 mV; p = 0.026）。最后，治疗动物的粘膜和粘膜下层组织学有明显改善。结论CISS治疗铜绿假单胞菌性家兔鼻窦炎具有较好的临床疗效。生物可降解支架表面双层药物涂层的创新设计可能为铜绿假单胞菌鼻窦炎提供比当前治疗策略更好的治疗优势。
Background Pseudomonas aeruginosa is common in chronic rhinosinusitus (CRS) and frequently resistant to antibiotic treatment. We recently described the ciprofloxacin and ivacaftor-releasing biodegradable sinus stent (CISS)?a drug-delivery system that administers ciprofloxacin and the mucociliary activator (ivacaftor) at high local concentrations with prolonged mucosal contact time and sustained delivery. The objective of this study is to evaluate the efficacy of the CISS in a rabbit model of P aeruginosa (PAO1 strain) sinusitis. Methods Ciprofloxacin/ivacaftor (double layer) was coated on biodegradable poly-D/L-lactic acid (PLLA). A total of 10 sinus stents (5 bare PLLA stent controls, 5 CISSs) were placed unilaterally in rabbit maxillary sinuses via dorsal sinusotomy after inducing infection for 1 week with PAO1. Animals were assessed 3 weeks after stent insertion with sinus culture, nasal endoscopy, computed tomography scan, histopathology, and in-vivo sinus potential difference (SPD) assay. Results Rabbits treated with CISS had significant reductions in computed tomography ( increment Kerschner scale: control, 0.55 +/- 0.92; CISS, -5.92 +/- 1.69; p = 0.024) and endoscopy (control, 4.0 +/- 0.0; CISS, 1.875 +/- 0.74; p = 0.003) scores. A 2-log reduction of PAO1 was observed (control, -2.14 +/- 0.77; CISS, 1.84 +/- 1.52; p = 0.047). SPD revealed significantly increased Cl- transport in the CISS group compared with the control group (Cl--free + forskolin Delta PD: control, -4.23 +/- 1.04 mV; CISS, -18.36 +/- 6.31 mV; p = 0.026). Finally, marked improvements were noted in the histology of the mucosa and submucosa in treated animals. Conclusion The CISS had robust clinical efficacy in treating P aeruginosa rabbit sinusitis. The innovative design of double-layered drug coating on the surface of the biodegradable stent may provide therapeutic advantages over current treatment strategies for P aeruginosa sinusitis.