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 (3mg) were uniformly coated on the surface of the PLLA stents. The CASS showed ciprofloxacin/azithromycin sustained release patterns, with 80.55 +/-11.
Background: Pseudomonas aeruginosa is common in chronic rhinosinusitus (CRS) and frequently resistant to antibiotic treatment. We recently described the ciprofloxacin and ivaca or-releasing biodegradable sinus stent (CISS)a drug-delivery system that administers ciprofloxacin and the mucociliary activator (ivaca or) 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/ivaca or (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 a er inducing infection for 1 week with PAO1. Animals were assessed 3 weeks a er 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 ( 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 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. C 2019 ARS-AAOA, LLC. How to Cite this Article:Lim D-J, McCormick J, Skinner D, et al. Controlled delivery of ciprofloxacin and ivaca or via sinus stent in a preclinical model of Pseudomonas sinusitis. Int Forum Allergy Rhinol. 2020;10:481-488.P seudomonas aeruginosa is one of the most common causes of chronic, biofilm-based sinus infection in
Objective Spontaneous cerebrospinal fluid (CSF) leaks represent a unique subset of skull base pathology and require distinctive management. Perioperative evaluation and management of intracranial hypertension are essential in preventing further erosion of the skull base and development of recurrent leak. The objective of this study is to evaluate the safety and utility of an expedited protocol for recording and managing intracranial hypertension following endoscopic repair of spontaneous CSF leaks. Methods Prospectively collected data was reviewed in patients undergoing endoscopic repair of spontaneous CSF leaks between January 2017 and March 2020. A standard intracranial pressure monitoring protocol was compared to an expedited protocol (EP), and data regarding the two groups was compared for leak location, short‐term success of skull base repair, complications, hospital length of stay, and cost‐based analysis. Results Fifty‐five patients (standard protocol, n = 28 vs. EP, n = 27) were included in the study. Leak location was similar between cohorts, with the lateral recess being the most common locations in both groups (37.9% vs. 40.6%; P = .90). Postoperative complications (3.6% vs. 7.4%; P = .53) and ventriculoperitoneal shunt rate (32.1% vs. 22.2%; P = .41) were similar among cohorts. There was no difference in lumbar drain complications (0% vs. 7.4%; P = .14) or recurrent leak (7.1% vs. 0%; P = .16). Length of stay was shorter in the EP group [median(interquartile range): 3(1) vs. 2 (1); P < .01]. Total hospital charges were similar between groups (median (USD/$1,000): 83.57 ± 49.58 vs. 83.93 ± 46.11; P = .18). Conclusion An expedited monitoring protocol shortened hospital stay without increased risk of complications. Level of Evidence III Laryngoscope, 131:E408–E412, 2021
Background Hypoxia due to closure at the ostiomeatal complex is widely considered one of the major pathogenic mechanisms leading to chronic inflammation in chronic rhinosinusitis (CRS). The objective of this study was to develop and characterize an oxygen‐generating biomaterial (OGB) as an innovative treatment strategy for CRS. Methods An OGB was fabricated by coating hydrophobic beeswax (BW, 15mg or 30mg) on the surface of calcium peroxide ‐ catalase complex (CPO‐CA, 30mg) and characterized using scanning electron microscopy (SEM). In vitro releases of both oxygen and hydrogen peroxide (H2O2) were spectrophotometrically quantified, and cytotoxicity in human sinonasal epithelial cells (HSNECs) was evaluated. The influence of OGB on transepithelial Cl– secretion was also determined by pharmacologically manipulating HSNECs, cultured under hypoxic conditions, in Ussing chambers. Results Three groups of OGBs: (1) CPO only; (2) CPO coated with CA and BW (1:1 ratio, CPO‐CA(1)‐BW(1)); and (3) CPO coated with CA and BW (1:0.5 ratio, CPO‐CA(1)‐BW(0.5) were analyzed for accumulated oxygen release over 7 days: highest release (mmol/mg) was observed in CPO‐CA(1)‐BW(1) = 0.11 ± 0.003, followed by CPO‐CA(1)‐BW(0.5) = 0.08 ± 0.010, and CPO = 0.05 ± 0.004 (p < 0.0001). H2O2 production (mM) was significantly higher in CPO (1.87 ± 0.50) compared to CPO‐CA (1)‐BW(1) (0.00 ± 0.00) (p < 0.001) after 24 h. CPO‐CA(1)‐BW(1) showed significantly reduced cytotoxicity and increased Cl– transport compared to the CPO group. Conclusion A novel OGB (CPO‐CA‐BW complex) exhibited sustained oxygen release over 7 days without significant cytotoxicity after 24 h in vitro. Preclinical studies evaluating the efficacy of OGB in CRS are warranted, especially for potential therapy in an obstruction‐based CRS model.
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