skip to main content


Title: 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 againstPseudomonas 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 reducedP aeruginosabiofilm 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 againstP aeruginosa. Further studies evaluating the efficacy of CASS in a preclinical model are planned.

 
more » « less
NSF-PAR ID:
10458933
Author(s) / Creator(s):
 ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
International Forum of Allergy & Rhinology
Volume:
10
Issue:
1
ISSN:
2042-6976
Page Range / eLocation ID:
p. 121-127
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract

    Metal–organic frameworks (MOFs) have applications in numerous fields. However, the development of MOF‐based “theranostic” macroscale devices is not achieved. Here, heparin‐coated biocompatible MOF/poly(ε‐caprolactone) (PCL) “theranostic” stents are developed, where NH2‐Materials of Institute Lavoisier (MIL)‐101(Fe) encapsulates and releases rapamycin (an immunosuppressive drug). These stents also act as a remarkable source of contrast in ex vivo magnetic resonance imaging (MRI) compared to the invisible polymeric stent. The in vitro release patterns of heparin and rapamycin respectively can ensure a type of programmed model to prevent blood coagulation immediately after stent placement in the artery and stenosis over a longer term. Due to the presence of hydrolysable functionalities in MOFs, the stents are shown to be highly biodegradable in degradation tests under various conditions. Furthermore, there is no compromise of mechanical strength or flexibility with MOF compositing. The system described here promises many biomedical applications in macroscale theranostic devices. The use of MOF@PCL can render a medical device MRI‐visible while simultaneously acting as a carrier for therapeutic agents.

     
    more » « less
  2. Patients with percutaneous coronary intervention generally receive either bare metal stents or drug‐eluting stents to restore the normal blood flow. However, due to the lack of stent production with an individual patient in mind, the same level of effectiveness may not be possible in treating two different clinical scenarios. This study introduces for the first time the feasibility of a patient‐specific stenting process constructed from direct 3D segmentation of medical images using direct 3D printing of biodegradable polymer–graphene composite with dual drug incorporation. A biodegradable polymer–carbon composite is prepared doped with graphene nanoplatelets to achieve controlled release of combinatorics as anticoagulation and antirestenosis agents. This study develops a technology prototyped for personalized stenting. An in silico analysis is performed to optimize the stent design for printing and its prediction of sustainability under force exerted by coronary artery or blood flow. A holistic approach covering in silico to in situ–in vivo establishes the structural integrity of the polymer composite, its mechanical properties, drug loading and release control, prototyping, functional activity, safety, and feasibility of placement in coronary artery of swine.

     
    more » « less
  3. Objectives/Hypothesis

    Subglottic stenosis (SGS) results from dysregulated extracellular matrix deposition by laryngotracheal fibroblasts causing scar tissue formation following intubation. Recent work has highlighted a relationship between this inflammatory state and imbalances in the upper airway microbiome. Herein, we engineer novel drug‐eluting endotracheal (ET) tubes to deliver a model antimicrobial peptide Lasioglossin‐III (Lasio) for the local modulation of the microbiome during intubation.

    Study Design

    Controlledin vitrostudy.

    Methods

    ET tubes were coated with a water‐in‐oil (w/o) emulsion of Lasio in poly(d,l‐lactide‐co‐glycolide) (PLGA) by dipping thrice. Peptide release was quantified over 2 weeks via fluorometric peptide assays. The antibacterial activity was tested against airway microbes (Staphylococcus epidermidis,Streptococcus pneumoniae, and pooled human microbiome samples) by placing Lasio/PLGA‐coated tubes and appropriate controls in 48 well plates with diluted bacteria. Bacterial inhibition and tube adhesion were tested by measuring optical density and colony formation after tube culture, respectively. Biocompatibility was tested against laryngotracheal fibroblasts and lung epithelial cells.

    Results

    We achieved a homogeneous coating of ET tubes with Lasio in a PLGA matrix that yields a prolonged, linear release over 1 week (typical timeframe before the ET tube is changed). We observed significant antibacterial activity againstS. epidermidis,S. pneumoniae, and human microbiome samples, and prevention of bacterial adherence to the tube. Additionally, the released Lasio did not cause any cytotoxicity toward laryngotracheal fibroblasts or lung epithelial cellsin vitro.

    Conclusion

    Overall, we demonstrate the design of an effective‐eluting ET tube to modulate upper‐airway bacterial infections during intubation which could be deployed to help prevent SGS.

    Level of Evidence

    NALaryngoscope, 132:1356–1363, 2022

     
    more » « less
  4. Abstract

    For degradable magnesium (Mg) alloy‐based stents it would be desirable to delay early corrosion to maintain mechanical strength. Similarly, early after stent placement reduced thrombogenicity is an important feature, while chronically, endothelial cell adhesion and vessel integration are desirable. In this study, surface eroding polymers of amino‐grafted poly(1,3‐trimethylene carbonate) (PTMC‐NH2) and PTMC‐NH2combined with sulfobetaine bearing polymer PSB (PTMC‐NHCO‐PSB) are developed, and these polymers are covalently attached onto 6‐phosphonohexanoic acid (PHA)‐coated AZ31 Mg alloy surfaces in sequence. In vitro degradation testing in ovine plasma shows PTMC, PTMC‐NH2, and PTMC‐NHCO‐PSB cast films experience a gradual thickness and mass loss with maintenance of smooth surfaces, confirming surface erosion behavior. The PTMC‐NH2polymer is firmly bound to the PHA‐modified AZ31 surface and demonstrates a resistance to peeling. PTMC, PTMC‐NH2, and PTMC‐NHCO‐PSB coated AZ31 have a lower corrosion rate versus polylactide‐co‐glycolide coated and untreated AZ31. PTMC‐NHCO‐PSB coated AZ31 inhibits platelet deposition and smooth muscle cell adhesion and growth, but after 2‐week immersion in plasma, this surface supports endothelial cell adhesion and growth. These results suggest PTMC‐NHCO‐PSB surface eroding coating offers a means of controlling corrosion while providing a temporally varying bio‐functionality for biodegradable vascular stent applications.

     
    more » « less
  5. Background

    The purpose of this retrospective review was to determine how patient‐related factors and culture data affect neo‐osteogenesis in patients with chronic rhinosinusitis (CRS) and patients with cystic fibrosis (CF) with CRS.

    Methods

    Information from a database associated with a large tertiary medical center was used to assess adult patients with CF CRS and non‐CF CRS (total, n = 102; CF CRS, n = 31; non‐CF CRS, n = 71). Radiologic evidence of neo‐osteogenesis was measured using the Global Osteitis Scoring Scale (GOSS), and mucosal disease was assessed using the Lund‐Mackay score (LMS) by 2 independent reviewers who were blinded to the patient's disease state. Bacterial cultures were obtained endoscopically. Multiple logistic regression models were used to evaluate the effect of age, sex, number of previous surgeries, CF, and culture species on the odds of neo‐osteogenesis.

    Results

    Fifty‐one of the 102 patients (50%) met radiologic criteria for neo‐osteogenesis. Sixty‐nine patients (67.6%) with CF CRS and non‐CF CRS had culture data. In the multiple logistic regression model, male gender was significantly associated with neo‐osteogenesis (odds ratio [OR], 5.2; 95% confidence interval [CI], 1.68‐17.86;p= 0.006).Pseudomonas aeruginosawas not associated with neo‐osteogenesis (OR, 3.12; 95% CI, 0.84‐12.80;p= 0.097). Age, number of surgeries, CF,Staphylococcus aureus, and coagulase‐negativeStaphylococcuswere not statistically significant.

    Conclusion

    To our knowledge, this is the first study to assess risk factors associated with neo‐osteogenesis and patients with CF CRS. Interestingly, male gender was the only significant predictor of neo‐osteogenesis.

     
    more » « less