Computational analysis of a 3D mucociliary clearance model predicting nasal drug uptake

Chari, Sriram; Sridhar, Karthik; Walenga, Ross; Kleinstreuer, Clement

doi:10.1016/j.jaerosci.2021.105757

Cited by 18 publications

(12 citation statements)

References 59 publications

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“…The rate of MCC is determined using the saccharin test [12]. The importance of MCC variations affected by different nasal cavities was evaluated by some researchers [43,[46][47][48]. It was concluded a 3D shell surface models led to a closer prediction of MCC rate against the experimental data [12].…”

Section: Introductionmentioning

confidence: 99%

Effects of continuous and discrete boundary conditions on the movement of upper-convected maxwell and Newtonian mucus layers in coughing and sneezing

Modaresi

Shirani

2022

Eur. Phys. J. Plus

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Mucociliary clearance is an important phenomenon inside the respiratory system as a first defensive mechanism against pathogens. Therefore, any assumption considered for the mucociliary clearance and affects its functionality must be validated. The present research deals with the effects of boundary conditions on the movement of upper-convected Maxwell and high viscosity Newtonian mucus layers, numerically. Furthermore, the validity of replacing the viscoelastic mucus layer with a high viscosity Newtonian layer is evaluated. The airway surface liquid layer is considered a two-layer model including non-Newtonian mucus and Newtonian periciliary layers. Four cyclic boundary conditions are imposed at the mucus-periciliary interface as the cilia movement to obtain variations of mucociliary clearance. The upper boundary of the mucus layer is also exposed to different shear stress levels including free slip, cough, and sneeze conditions. By investigation of velocity variations inside mucus and periciliary layers, it is concluded the differences between viscoelastic and Newtonian mucus are not negligible. The maximum velocity differences between the two fluids are more than 52% and 215% during cough and sneeze, respectively. The results show there is a high order of dependency between the relaxation time and the imposed boundary conditions at the mucus-periciliary interface that leads to the invalidation of replacing two fluids with each other. Moreover, the results show substituting the viscoelastic mucus with a high viscosity Newtonian one depends on the mucus-periciliary interface boundary condition. If an independent time-varying boundary condition is used, the substitution leads to an error less than 7% under different shear stress levels. However, time-varying boundary condition shows 38% and 88% differences between high viscosity Newtonian and viscoelastic mucus layers. Furthermore, neglecting the recovery stroke leads to a velocity underestimation up to 50% by substituting viscoelastic mucus with a high viscosity Newtonian one. Therefore, replacing the viscoelastic mucus with a high viscosity Newtonian one is not acceptable for numerical simulations.

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Section: Introductionmentioning

confidence: 99%

Effects of continuous and discrete boundary conditions on the movement of upper-convected maxwell and Newtonian mucus layers in coughing and sneezing

Modaresi

Shirani

2022

Eur. Phys. J. Plus

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“…When the posterior region was split into multiple smaller surfaces based on turbinates, the sub-regional surfaces had relatively smaller surface areas, and the liquid masses were shown to accumulate at the sub-regional boundaries. The agreement between the prediction and the in vitro measurement was improved when the surfaces were re-grouped to upper and lower posterior regions, considering mucociliary clearance from front to back of the nasal cavity [ 48 , 66 , 67 , 102 ].…”

Section: Discussionmentioning

confidence: 99%

“…In vitro testing using realistic nasal airway geometries may also help to understand the geometrical factors influencing drug delivery to different regions of the nose [ 7 , 11 , 13 , 14 , 16 , 18 , 19 , 20 , 22 , 39 , 40 , 41 , 42 , 43 ]. In silico testing using computational fluid dynamics (CFD) simulations can provide detailed information on device performance and nasal deposition, and CFD models combined with pharmacokinetic models can provide additional information on systemic drug plasma concentration, while limiting time and cost associated with the testing [ 5 , 9 , 24 , 25 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ].…”

Section: Introductionmentioning

confidence: 99%

“…In a subsequent study, the authors investigated the effects of head tilt on liquid motion and its impact on wall stress using the computational Volume of Fluid approach [ 63 , 64 , 65 ]. As shown by Rygg et al [ 44 , 45 , 66 ], Shang et al [ 67 , 68 ] and Chari et al [ 48 ], mucociliary clearance of the mucus layer on the nasal surface can lead to further increase in spray liquid motion, but over a longer time period. In view of in vitro testing of nasal sprays, spray–wall interaction with post-impaction liquid motion are principal factors of interest that may impact the regional distribution of drugs within the nose.…”

Section: Introductionmentioning

confidence: 99%

“…The SWI-PDLM model developed in this study is intended to capture in vitro nasal spray test conditions and is compared with corresponding in vitro data. As a result, mucociliary clearance effects that occur in vivo over longer time scales, as previously simulated by Rygg et al [ 44 , 45 , 66 ], Shang et al [ 67 , 68 ] and Chari et al [ 48 ] were not included. It is anticipated that in many nasal spray delivery cases, the spray–wall interaction and post-deposition liquid motion largely control the final anterior to posterior distribution of the nasal spray delivery.…”

Section: Introductionmentioning

confidence: 99%

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Importance of Spray–Wall Interaction and Post-Deposition Liquid Motion in the Transport and Delivery of Pharmaceutical Nasal Sprays

et al. 2022

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Nasal sprays, which produce relatively large pharmaceutical droplets and have high momentum, are primarily used to deliver locally acting drugs to the nasal mucosa. Depending on spray pump administration conditions and insertion angles, nasal sprays may interact with the nasal surface in ways that creates complex droplet–wall interactions followed by significant liquid motion after initial wall contact. Additionally, liquid motion can occur after deposition as the spray liquid moves in bulk along the nasal surface. It is difficult or impossible to capture these conditions with commonly used computational fluid dynamics (CFD) models of spray droplet transport that typically employ a deposit-on-touch boundary condition. Hence, an updated CFD framework with a new spray–wall interaction (SWI) model in tandem with a post-deposition liquid motion (PDLM) model was developed and applied to evaluate nasal spray delivery for Flonase and Flonase Sensimist products. For both nasal spray products, CFD revealed significant effects of the spray momentum on surface liquid motion, as well as motion of the surface film due to airflow generated shear stress and gravity. With Flonase, these factors substantially influenced the final resting place of the liquid. For Flonase Sensimist, anterior and posterior liquid movements were approximately balanced over time. As a result, comparisons with concurrent in vitro experimental results were substantially improved for Flonase compared with the traditional deposit-on-touch boundary condition. The new SWI-PDLM model highlights the dynamicenvironment that occurs when a nasal spray interacts with a nasal wall surface and can be used to better understand the delivery of current nasal spray products as well as to develop new nasal drug delivery strategies with improved regional targeting.

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Modeling and simulation in drug delivery

Bandara

Gamage

Gunaratne

et al. 2023

Novel Platforms for Drug Delivery Applications

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Computational analysis of a 3D mucociliary clearance model predicting nasal drug uptake

Cited by 18 publications

References 59 publications

Effects of continuous and discrete boundary conditions on the movement of upper-convected maxwell and Newtonian mucus layers in coughing and sneezing

Effects of continuous and discrete boundary conditions on the movement of upper-convected maxwell and Newtonian mucus layers in coughing and sneezing

Importance of Spray–Wall Interaction and Post-Deposition Liquid Motion in the Transport and Delivery of Pharmaceutical Nasal Sprays

Modeling and simulation in drug delivery

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