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

Lara Leclerc 1, 2, 3, * Jérémie Pourchez 1, 3 Gérald Aubert 4 Sandrine Leguellec 5, 6 Laurent Vecellio 5, 6 Michèle Cottier 1, 2 Marc Durand 1, 2
* Corresponding author
1 SFR IFRESIS - Structure Fédérative de Recherche - Institut Fédératif de Recherche en Sciences et Ingénierie de la Santé
2 LINA-ENSMSE - Laboratoire Interdisciplinaire d'Etude des Nanoparticules Aérosolisées
3 CIS-ENSMSE - Centre Ingénierie et Santé
4 Laboratoire Antibiologie
5 DTF-Aerodrug
6 Pathologies Respiratoires : Protéolyse et Aérosolthérapie
Abstract : Purpose: 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.
Keywords : drug deposition nasal replica Aerosol therapy maxillary sinuses
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Lara Leclerc, Jérémie Pourchez, Gérald Aubert, Sandrine Leguellec, Laurent Vecellio, et al.. 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. Pharmaceutical Research, American Association of Pharmaceutical Scientists, 2014, 31 (9), pp.2335-2343. ⟨http://link.springer.com/article/10.1007%2Fs11095-014-1330-6⟩. ⟨10.1007/s11095-014-1330-6⟩. ⟨emse-01110944⟩

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