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

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.

Herbal dry extract BNO 1011 improves clinical and mucociliary parameters in a rabbit model of chronic rhinosinusitis.

BACKGROUND: Enhancing chloride (Cl- ) secretion in sinus epithelia represents a novel therapeutic approach to chronic rhinosinusitis (CRS). Herbal dry extract BNO 1011 enhances mucociliary clearance (MCC) via upregulation of Cl- secretion in sinonasal cultures in vitro and murine epithelium in vivo. The objective of this study is to evaluate whether the BNO 1011 improves MCC and clinical parameters in a rabbit model of CRS. METHODS: After the development of CRS in 30 New Zealand white rabbits, animals were randomly assigned to receive oral placebo (n = 10), BNO 1011 (low dose [LD], 25 mg/kg/daily) (n = 10), or BNO1011 (high dose [HD], 125 mg/kg/daily) (n = 10) for 4 weeks. Outcomes included sinus opacification (Kerschner's rabbit sinus CT grade), maxillary epithelial Cl- secretion (sinus potential difference [PD] assay), airway surface liquid (ASL) depth using micro-optical coherence tomography (µOCT), and submucosal gland density (SMD) on histopathology. Outcome parameters were analyzed by 2 blinded investigators. RESULTS: BNO 1011 significantly cleared sinus opacification (HD = 1.21 ± 0.63, LD = 1.26 ± 0.37,) compared to placebo (4.02 ± 0.92) (p = 0.009). BNO 1011 resulted in markedly greater mean sinus PD polarization (HD = -12.23 ± 1.4 mV, LD = -12.0 ± 3.0 mV) when compared to rabbits treated with placebo (-4.1 ± 1.1 mV) (p = 0.03). ASL depth was significantly improved when treated with HD (4.08 ± 0.06 µm) and LD (4.05 ± 0.06 µm) compared to placebo (3.5 ± 0.05 µm) (post hoc analysis, p < 0.0001). Histologically, epithelial thickness (HD = 10.0 ± 0.7 µm; LD = 13.7 ± 0.9 µm; placebo = 21.1 ± 2.3 µm; p < 0.005), subepithelial thickness (HD = 63.1 ± 6.6 µm; LD = 103.2 ± 6.7 µm; placebo = 113.3 ± 6.0 µm; p < 0.001), and SMD (HD = 22.2 ± 2.9%; LD = 31.8 ± 1.1%; placebo = 43.8 ± 1.7%; p < 0.0001) were noticeably better with the HD. CONCLUSION: Herbal dry extract BNO 1011 improves radiographic, histologic, and MCC parameters in a rabbit model of CRS.