title: Impact of airborne particle size, acoustic airflow and breathing pattern on delivery of nebulized antibiotic into the maxillary sinuses using a realistic human nasal replica.
abstract: OBJECTIVE
  Improvement of clinical outcome in patients with sinuses disorders involves targeting delivery of nebulized drug into the maxillary sinuses. We investigated the impact of nebulization conditions (with and without 100 Hz acoustic airflow), particle size (9.9 μm, 2.8 μm, 550 nm and 230 nm) and breathing pattern (nasal vs. no nasal breathing) on enhancement of aerosol delivery into the sinuses using a realistic nasal replica developed by our team.
  
  
  METHODS
  After segmentation of the airways by means of high-resolution computed tomography scans, a well-characterized nasal replica was created using a rapid prototyping technology. A total of 168 intrasinus aerosol depositions were performed with changes of aerosol particle size and breathing patterns under different nebulization conditions using gentamicin as a marker.
  
  
  RESULTS
  The results demonstrate that the fraction of aerosol deposited in the maxillary sinuses is enhanced by use of submicrometric aerosols, e.g. 8.155 ± 1.476 mg/L of gentamicin in the left maxillary sinus for the 2.8 μm particles vs. 2.056 ± 0.0474 for the 550 nm particles. Utilization of 100-Hz acoustic airflow nebulization also produced a 2- to 3-fold increase in drug deposition in the maxillary sinuses (e.g. 8.155 ± 1.476 vs. 3.990 ± 1.690 for the 2.8 μm particles).
  
  
  CONCLUSIONS
  Our study clearly shows that optimum deposition was achieved using submicrometric particles and 100-Hz acoustic airflow nebulization with no nasal breathing. It is hoped that our new respiratory nasal replica will greatly facilitate the development of more effective delivery systems in the future.
authors.affiliation: Laboratoire Interdisciplinaire d'étude des Nanoparticules Aérosolisées (LINA - EA 4624), Faculté de Médecine Jacques Lisfranc, Université Jean Monnet, 15 rue Ambroise Paré, 42023, Saint-Etienne, France, lara.leclerc@univ-st-etienne.fr.
authors.forename: Lara
authors.initials: L
authors.lastname: Leclerc
authors.forename: Jérémie
authors.initials: J
authors.lastname: Pourchez
authors.forename: Gérald
authors.initials: G
authors.lastname: Aubert
authors.forename: Sandrine
authors.initials: S
authors.lastname: Leguellec
authors.forename: Laurent
authors.initials: L
authors.lastname: Vecellio
authors.forename: Michèle
authors.initials: M
authors.lastname: Cottier
authors.forename: Marc
authors.initials: M
authors.lastname: Durand
mesh_terms: D000162:Acoustics; D000281:Administration, Intranasal; D000328:Adult; D000336:Aerosols / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D004867:Equipment Design; D005839:Gentamicins / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D008297:Male; D008443:Maxillary Sinus / Q000033:anatomy & histology / Q000502:physiology*; D008953:Models, Anatomic; D009330:Nebulizers and Vaporizers; D009666:Nose / Q000033:anatomy & histology / Q000502:physiology; D010316:Particle Size; D012119:Respiration
chemical_list: D000336:Aerosols; D000900:Anti-Bacterial Agents; D005839:Gentamicins