Airflow and nanoparticle deposition in rat nose under various breathing and sniffing conditions: a computational evaluation of the unsteady effect.

Accurate prediction of nanoparticle (1~100 nm) deposition in the rat nasal cavity is important for assessing the toxicological impact of inhaled nanoparticles as well as for potential therapeutic applications. A quasi-steady assumption has been widely adopted in the past investigations on this topic, yet the validity of such simplification under various breathing and sniffing conditions has not been carefully examined. In this study, both steady and unsteady computational fluid dynamics (CFD) simulations were conducted in a published rat nasal model under various physiologically realistic breathing and sniffing flow rates. The transient airflow structures, nanoparticle transport and deposition patterns in the whole nasal cavity and the olfactory region were investigated and compared with steady state simulation of equivalent flow rate. The results showed that (1) the quasi-steady flow assumption for cyclic flow was valid for over 70% of the cycle period during all simulated breathing and sniffing conditions in the rat nasal cavity, or the unsteady effect was only significant during the transition between the respiratory phases; (2) yet the quasi-steady assumption for nanoparticle transport was not valid, except in the vicinity of peak respiration. In general, the total deposition efficiency of nanoparticle during cyclic breathing would be lower than that of steady state due to the unsteady effect on particle transport and deposition, and further decreased with the increase of particle size, sniffing frequency, and flow rate. In the contrary, previous study indicated that for micro-scale particles (0.5~4μm), the unsteady effect would increase deposition efficiencies in rat nasal cavity. Combined, these results suggest that the quasi-steady assumption of nasal particle transport during cycling breathing should be used with caution for an accurate assessment of the toxicological and therapeutic impact of particle inhalation. Empirical equations and effective steady state approximation derived in this study are thus valuable to estimate such unsteady effects in future applications.

[1]  M. M. Mozell,et al.  Modeling inspiratory and expiratory steady-state velocity fields in the Sprague-Dawley rat nasal cavity. , 2007, Chemical senses.

[2]  B. Asgharian,et al.  Deposition of fine and coarse aerosols in a rat nasal mold. , 2001, Inhalation toxicology.

[3]  Y. Cheng,et al.  In vivo deposition of ultrafine aerosols in the nasal airway of the rat. , 1991, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[4]  Thomas Heistracher,et al.  Local particle deposition patterns may play a key role in the development of lung cancer. , 2003, Journal of applied physiology.

[5]  J. Kimbell,et al.  Deposition of inhaled nanoparticles in the rat nasal passages: Dose to the olfactory region , 2009, Inhalation toxicology.

[6]  Baruch B. Lieber,et al.  Oscillatory Flow in a Symmetric Bifurcation Airway Model , 1998, Annals of Biomedical Engineering.

[7]  R D Kamm,et al.  Gas flow and mixing in the airways , 1994, Critical care medicine.

[8]  R. H. Gray,et al.  Deposition and retention of inhaled aggregate 67Ga2O3 particles in beagle dogs, Fischer-344 rats, and CD-1 mice. , 1984, American Industrial Hygiene Association journal.

[9]  K T Morgan,et al.  Computer simulation of inspiratory airflow in all regions of the F344 rat nasal passages. , 1997, Toxicology and applied pharmacology.

[10]  C. Kleinstreuer,et al.  Airflow structures and nano-particle deposition in a human upper airway model , 2004 .

[11]  S. Patankar.  Numerical Heat Transfer and Fluid Flow , 2018, Lecture Notes in Mechanical Engineering.

[12]  U. Kompella,et al.  Nasal route for direct delivery of solutes to the central nervous system: fact or fiction? , 1998, Journal of drug targeting.

[13]  T. Martonen,et al.  Simulation of aerosol deposition in extrathoracic and laryngeal passages of the laboratory rat , 1993 .

[14]  H. Chang,et al.  Steady and oscillatory transnasal pressure-flow relationships in healthy adults. , 1991, Journal of applied physiology.

[15]  P. Dalton,et al.  Numerical modeling of turbulent and laminar airflow and odorant transport during sniffing in the human and rat nose. , 2006, Chemical senses.

[16]  J. Grotberg,et al.  An analysis of pollutant gas transport and absorption in pulmonary airways. , 1990, Journal of biomechanical engineering.

[17]  C Kleinstreuer,et al.  Laminar airflow and nanoparticle or vapor deposition in a human nasal cavity model. , 2006, Journal of biomechanical engineering.

[18]  D. Wilcox.  Turbulence modeling for CFD , 1993 .

[19]  D Isabey,et al.  Steady and unsteady pressure-flow relationships in central airways. , 1981, Journal of applied physiology: respiratory, environmental and exercise physiology.

[20]  K T Morgan,et al.  Studies of inspiratory airflow patterns in the nasal passages of the F344 rat and rhesus monkey using nasal molds: relevance to formaldehyde toxicity. , 1991, Toxicology and applied pharmacology.

[21]  M. M. Mozell,et al.  Numerical modeling of odorant uptake in the rat nasal cavity. , 2007, Chemical senses.

[22]  W. Kreyling,et al.  Translocation of Inhaled Ultrafine Particles to the Brain , 2004, Inhalation toxicology.

[23]  J. West.  Bioengineering aspects of the lung , 1977 .

[24]  Kevin R Minard,et al.  Application of Magnetic Resonance (MR) Imaging for the Development and Validation of Computational Fluid Dynamic (CFD) Models of the Rat Respiratory System , 2006, Inhalation toxicology.

[25]  P. Moin,et al.  A dynamic subgrid‐scale eddy viscosity model , 1990 .

[26]  J. Scott,et al.  Responses of the rat olfactory epithelium to retronasal air flow. , 2007, Journal of neurophysiology.

[27]  David E. Hornung,et al.  A quantitative analysis of sniffing strategies in rats performing odor detection tasks , 1987, Physiology & Behavior.

[28]  R C Schroter,et al.  Flow patterns in models of the human bronchial airways. , 1969, Respiration physiology.

[29]  J. Womersley.  Method for the calculation of velocity, rate of flow and viscous drag in arteries when the pressure gradient is known , 1955, The Journal of physiology.

[30]  Y. Cheng,et al.  Deposition of ultrafine aerosols in rat nasal molds. , 1990, Toxicology and applied pharmacology.

[31]  Ryan M Carey,et al.  A method for generating natural and user-defined sniffing patterns in anesthetized or reduced preparations. , 2008, Chemical senses.

[32]  B. Asgharian,et al.  In vivo measurement of fine and coarse aerosol deposition in the nasal airways of female Long-Evans rats. , 2001, Toxicological sciences : an official journal of the Society of Toxicology.

[33]  L. Illum.  Nasal drug delivery: new developments and strategies. , 2002, Drug discovery today.