Understanding the flow behaviour in human maxillary sinuses for drug delivery applications
| dc.contributor.advisor | Arjomandi, Maziar | |
| dc.contributor.advisor | Cazzolato, Benjamin | |
| dc.contributor.advisor | Tian, Zhao Feng | |
| dc.contributor.author | Pourmehran, Oveis | |
| dc.contributor.school | School of Mechanical Engineering | en |
| dc.date.issued | 2021 | |
| dc.description.abstract | The sinus infection, chronic rhinosinusitis (CRS), has a prevalence ranging from 4.9% to 10.9% worldwide. When a nasal cavity (NC) is exposed to pathogens carried by inhaled aerosols, the attached sinuses, especially the maxillary sinus (MS), are highly prone to infection. The MS, a hollow organ attached to the NC, plays the role of thermal insulation in a human skull and affects the quality of the human voice. The only opening, which connects the NC to the MS, is a circular slit-like opening called the ostium, with a channel of <5 mm in diameter. The narrowness of the ostium is a significant challenge for drug delivery to the MS for the treatment of CRS. Various non-invasive devices, including nasal sprays and jet nebulizers, are available for drug delivery to the MS; however, due to the poor accessibility of the MS and the narrowness of the ostium, the efficiency of drug delivery to the MS is very low. Acoustic drug delivery (ADD) is a modern pathway for topical drug delivery to the MS, demonstrated to enhance drug delivery. This technology, using a fixed acoustic frequency, is currently available as a pre/post-surgical therapy but has not been able to demonstrate the full potential of delivering sufficient drug particles to the sinuses in most CRS cases. Several researchers investigated the effects of fixed acoustic frequencies, 45 Hz and 100 Hz, and reported an increase of 2 to 3-fold in the aerosol deposition in the MS when compared with conventional drug delivery. However, it has recently been hypothesised that the underlying mechanism of ADD is based on the Helmholtz resonator principle, where the air plug in the ostium oscillates when an external acoustic field is applied to the nostril. Oscillation of the air plug in the ostium leads to the delivery of the aerosols (nebulised drugs) from the NC to the MS. Accordingly, the maximum delivery of aerosols into the MS occurs when the amplitude of the oscillation of the air plug in the ostium is maximized. The maximum amplitude of the oscillation of the air plug in the ostium occurs at the resonance frequency of the NC-MS combination. In a limited number of the studies, the equation for a Helmholtz resonator (derived for a combination of a spherical cavity and a cylindrical neck), was used for predicting the resonance frequency of the NC-MS combination, which was superimposed onto the nebulised medication entering the nostril. Under this method, the efficiency of drug delivery to the MS increased 5-fold at most, when compared with non-acoustic drug delivery. In a more recent study, an acoustic frequency sweep was applied to the nostril, which showed a 10-fold increase in the aerosol deposition in the MS compared with conventional drug delivery. Such an increase in drug delivery efficiency is still insufficient for the treatment of CRS. Hence, it is important to predict the resonance frequency of the NC-MS combination accurately to increase the ADD efficiency significantly. The main aim of this thesis is to improve the efficiency of ADD to the MS by application of targeted excitation frequencies of the NC-MS combination to the nostril. Initially, the resonance frequency of an NC-MS combination was predicted as accurately as possible, and then the effect of various acoustic frequencies on ADD efficiency was investigated. In this thesis, several numerical models were explored, along with experimental testing. The numerical models include finite element analysis (FEA), computational fluid dynamics (CFD), and the Helmholtz resonator equation. The resonance frequencies of several simplified NC-MS combinations were predicted by this numerical model and compared with the experimental data to determine the most accurate numerical model. It was found that the Helmholtz resonator equation and FEA overpredict the resonance frequency of the NC-MS combination by 41% (depending on the size of the ostium and MS) compared with the experimental data. The CFD approach underpredicted the resonance frequency of the NC-MS combination by 8% compared with in-house experimental data, which proved to be the most accurate amongst the explored numerical models. The application of the Helmholtz resonator equation and FEA were shown not to provide an accurate prediction of the resonance frequency of the NC-MS combination because the equations of the Helmholtz resonator and the linearised Eulerian equation used in FEA do not account for the effect of the shape of the MS and the presence of the NC, while the Navier-Stokes equation used in CFD does. Using the CFD model, the effect of geometrical parameters such as the ostium length/diameter, MS shape/volume, and the NC width on the resonance frequency of an NC-MS combination were also studied. To examine the importance of the resonance frequency of the NC-MS combination on the ADD efficiency, a CFD model was developed to investigate the effect of various input frequencies, including the resonance and off-resonance frequencies, on the transport of particles from NC to the MS using an Eulerian-Lagrangian particle tracking scheme. Moreover, the effect of amplitude of the acoustic source and the inlet flow rate (at the nostril) on the transport of particles from the NC to the MS were investigated using a CFD model in a simplified NC-MS combination. The results showed that the highest transport of particles from the NC to the MS occurred when the inlet frequency was identical to the resonance frequency. It has been shown that the amplitude of the acoustic source has a monotonic relationship with the transport of particles from the NC to the MS; however, the airflow rate has an inverse relationship with it. Moreover, the effect of particle diameters and density on the penetration of particles in the MS were investigated using CFD modelling. It was found that increasing the particle diameter and density decreases the penetration of particles into the MS; the reason is that, in the presence of an acoustic field, increasing the particle diameter/density decreases the particle entrainment coefficient, which increases the acoustic Stokes number. An increase in the Stokes number reduces the ability of the particles to follow the oscillation of the air plug in the ostium with an amplitude identical to that of fluid. To explore the feasibility of ADD in practice, a 3D printed model of a realistic NC-MS combination was used to conduct the experiments to investigate the effect of resonance frequency on particle deposition in the MS, where a 2.5% sodium fluoride (NaF) was used to as the drug tracer. A loudspeaker was used to generate the acoustic field of interest, which was then applied to the nostril. The results show that when an acoustic field at a frequency equal to the resonance frequency of the NC-MS (obtained experimentally) is applied to the nostril, the particle deposition in the MS increases by 75-fold when compared with conventional drug delivery. The effect of input acoustic amplitude on particle deposition was also studied using a 3D printed model. The experimental data shows that increasing the input acoustic amplitude increases the particle deposition in the MS; however, increasing the amplitude above 120dB does not have a significant effect on the deposition. This might imply that at certain acoustic amplitudes a saturation point for aerosol deposition is reached. In the CFD simulation for a realistic NC-MS model, it was found that in the presence of an external acoustic field, not only does the air plug in the ostium oscillate but also a portion of the air plug in the middle meatus oscillates. Hence, to increase the ADD efficiency, it is important to transport particles to the middle meatus as much as possible. To do so, the effect of inlet flow parameters, as well as the impact of the diameter of the nozzle that injects the particles at the nostril, on the drug delivery to MM-Ostium regions was investigated. The term MM-Ostium refers to a region in the middle meatus (MM) where the ostium connects the MM to the MS. An increase in particle retention criterion in the MM-Ostium region was calculated to quantify the increase in the drug delivery to the MS region. The results have shown that the effect of turbulence at the inlet of the NC on drug delivery to the MM-Ostium region is negligible. It was also demonstrated that increasing the flow swirl at the inlet improves the total particle deposition due to the generation of centrifugal force, which acts on the particles in the nostril and vestibule. The results also suggest that drug delivery efficiency to the MS can be increased by using a swirling flow with a moderate swirl number of 0.6. Finally, it was found that decreasing the nozzle diameter can increase drug delivery to the MM-Ostium region, which subsequently increases the drug delivery to the MS. | en |
| dc.description.dissertation | Thesis (Ph.D.) -- University of Adelaide, School of Mechanical Engineering, 2021 | en |
| dc.identifier.uri | https://hdl.handle.net/2440/133579 | |
| dc.language.iso | en | en |
| dc.provenance | This electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at: http://www.adelaide.edu.au/legals | en |
| dc.subject | Acoustic drug delivery | en |
| dc.subject | CFD | en |
| dc.subject | Maxillary sinus | en |
| dc.title | Understanding the flow behaviour in human maxillary sinuses for drug delivery applications | en |
| dc.type | Thesis | en |
Files
Original bundle
1 - 1 of 1
No Thumbnail Available
- Name:
- Pourmehran2021_PhD.pdf
- Size:
- 31.65 MB
- Format:
- Adobe Portable Document Format