Nasal Deposition Efficiency Research Articles

Investigation of inter-subject variation in ultrafine particle deposition across human nasal airways: A study involving children, adults, and the elderly

The airflow and particle dynamics in adult nasal airways have been extensively investigated, but the impact of age-related anatomical changes in children and the elderly remains underexplored. This study systematically investigates age-related anatomical variations and associated influence on nasal airflow dynamics and ultrafine particle deposition characteristics by using Computational Fluid-Particle Dynamics (CFPD) approach. Numerical simulations were conducted for 9 healthy nasal subjects spanning a wide age range. 6 Nasal subjects from the Development Group were used as the primary models for data analysis and deposition correlation development, while 3 subjects from the Validation Group were used to validate the reliability of the derived total and subregional deposition correlations. Our results reveal distinctive variations across age groups. Specifically, the elderly and children exhibit unique patterns that differ from those of young adults. While total deposition efficiency differs significantly between children and adults, filtration efficiency in the subregion with most deposition, main respiratory, remains consistent. Lastly, overall and subregional empirical equations for deposition efficiency were developed by incorporating the combined diffusion parameter, Sca∆b, corroborating the use of geometrical characteristic parameters for each specific subject in predicting nasal deposition efficiency across different age groups. Our findings are expected to improve the predictive nanoparticle exposure analysis in nasal airways across different age groups, thereby improving the respiratory health for individuals throughout the life span.

Spray Dried Levodopa-Doped Powder Potentially for Intranasal Delivery.

This work was aimed to develop levodopa (L-dopa) nasal powder to achieve controllable drug release and high nasal deposition efficiency. A series of uniform microparticles, composed of amorphous L-dopa and excipients of hydroxypropyl methyl cellulose (HPMC), polyvinylpyrrolidone (PVP), or hydroxypropyl-β-cyclodextrin (CD), were fabricated by a self-designed micro-fluidic spray dryer. The effects of excipient type and drug/excipient mass ratio on the particle size, morphology, density, and crystal property, as well as the in vitro performance of drug release, mucoadhesion, and nasal deposition, were investigated. Increased amounts of added excipient, regardless of its type, could accelerate the L-dopa release to different extent. The addition of CD showed the most obvious effect, i.e., ~83% of L-dopa released in 60 min for SD-L1CD2, compared to 37% for raw L-dopa. HPMC could more apparently improve the particle mucoadhesion than PVP and CD, with respective adhesive forces of ~269, 111, and 26 nN for SD-L1H2, -L1P2, and -L1CD2. Nevertheless, the deposition fractions in the olfactory region for such samples were almost the same (~14%), probably ascribable to their quite similar particle aerodynamic diameter (~30 μm). This work demonstrates a feasible methodology for the development of nasal powder.

In-Vivo Measurements of Micrometer-Sized Particle Deposition in the Nasal Cavities of Taiwanese Adults

It has been observed that Asians and Caucasians possess considerably different craniofacial features, which may affect the anatomical structure of the upper respiratory tract and, consequently, the characteristics of particle deposition. Most deposition studies on the human respiratory tract were primarily based on a limited number of Caucasian subjects. Therefore, data of the particle deposition efficiency in the upper respiratory tract of Asians are needed to supplement the understanding of the deposition characteristics in the human respiratory tract. This study measured the nasal deposition efficiency of particles ranging from 0.5 to 20 μm in five Taiwanese male and four Taiwanese female adults under different inspiratory flow rates. The measured deposition efficiency showed a very large intersubject variability in the inertial parameters, ranging between 103 to 5 × 104 μm2 cm3/s, and the deposition efficiency of the subjects with similar values of the minimum nasal cross-sectional area approaches to ...

Deposition of inhaled nanoparticles in the rat nasal passages: Dose to the olfactory region

In vivo experiments have shown that nanoparticles depositing in the rat olfactory region can translocate to the brain via the olfactory nerve. Quantitative predictions of the dose delivered by inhalation to the olfactory region are needed to clarify this route of exposure and to evaluate the dose-response effects of exposure to toxic nanoparticles. Previous in vivo and in vitro studies quantified the percentage of inhaled nanoparticles that deposit in the rat nasal passages, but olfactory dose was not determined. The dose to specific nasal epithelium types is expected to vary with inhalation rate and particle size. The purpose of this investigation, therefore, was to develop estimates of nanoparticle deposition in the nasal and, more specifically, olfactory regions of the rat. A three-dimensional, anatomically accurate, computational fluid dynamics (CFD) model of the rat nasal passages was employed to simulate inhaled airflow and to calculate nasal deposition efficiency. Particle sizes from 1 to 100 nm and airflow rates of 288, 432, and 576 ml/min (1, 1.5, and 2 times the estimated resting minute volume) were simulated. The simulations predicted that olfactory deposition is maximum at 6–9% of inhaled material for 3- to 4-nm particles. The spatial distribution of deposited particles was predicted to change significantly with particle size, with 3-nm particles depositing mostly in the anterior nose, while 30-nm particles were more uniformly distributed throughout the nasal passages.

Untersuchungen zur nasalen Depositionseffizienz für Weizenmehl- und Maisstärke-Staub

In-vivo-evaluation of the nasal deposition efficiency is problematic, because a postnasal measurement of the dust particle concentration is difficult. A new method is represented, which measures in front of the nose the dust loading after ortho- and retronasal passage relative easily. 36 healthy subjects were nasally dust-exposed sitting in an exposure chamber. With the help of dust sampling system (Respicon) the particle size-referred dust loading before and after the nasal airflow passage was gravimetrically determined. The constant flow rate was 3.111 per minute. A contamination with breathing air was excluded by an active velopharyngeal closure. The subjects breathed orally over a breathing tube clean air. They were in each case 15 min exposed to the constant pre-nasal wheaten flour or corn starch dust produced over a brush disperser (Palas, RBG 1000). The time interval between both exposures was seven days excluding cross over effects. The deposition efficiency of both types of food powder was particle size dependent. Highest it was -as expected- with the particle sizes between 5-100 microm. Here it lay between 92% and 99%. The small particles of wheaten flour respective corn starch with an aerodynamic diameter between 1-4 microm deposited nasally 31% respectively 74%. The new relatively simple method of measurement of nasal deposition efficiency does not load the deeper respiratory tract. The results confirm the good filtering capability of the healthy nose for large dust particles. The nasal deposition of particles smaller than 5 microm is reduced but not absent. The small dust particles of wheaten flour and corn starch are very different nasally deposited. The different electrostatic charges of the two food powders may explain these differences.

Nasal Contribution to Breathing and Fine Particle Deposition in Children Versus Adults

Both the route of breathing, nasal versus oral, and the effectiveness of the nose to filter inhaled, fine particles may differ between children and adults. This study compared (1) the nasal contribution to breathing at rest and during mild to moderate exercise in children (age 6–10 yr) versus young adults and (2) the nasal deposition efficiency (NDE) of fine particles (1 and 2 μm MMAD, GSD < 1.2) under resting and light exercise breathing conditions in the same children and adults. Nasal contribution to breathing was assessed by respiratory inductance plethysmography and a nasal mask with flow meter during incremental exercise on a bicycle ergometer. Fine particle deposition fractions for nasal and oral breathing were assessed by inhalation of monodisperse carnauba wax particles and laser photometry to determine inhaled/exhaled concentrations. There was a trend for children to have a lesser nasal contribution to breathing at rest and during exercise, but the differences from adults were not statistically significant. Children did, however, have significantly decreased NDE for 2-μm particles under light exercise breathing conditions compared to adults, suggesting less efficient nasal filtering for larger particles and higher flow conditions. These results suggest that the lungs of children may be exposed to higher concentrations of inhaled, ambient particles than adults.

The Influence of Spray Properties on Intranasal Deposition

While numerous devices, formulations, and spray characteristics have been shown to influence nasal deposition efficiency, few studies have attempted to identify which of these interacting factors plays the greatest role in nasal spray deposition. The deposition patterns of solutions with a wide range of surface tensions and viscosities were measured using an MRI-derived nasal cavity replica. The resulting spray plumes had angles between 29 degrees and 80 degrees and contained droplet sizes (D(v50)) from 37-157 microm. Each formulation contained rhodamine 590 as a fluorescent marker for detection. Administration angles of 30 degrees , 40 degrees , or 50 degrees above horizontal were tested to investigate the role of user technique on nasal deposition. The amount of spray deposited within specific regions of the nasal cavity was determined by disassembling the replica and measuring the amount of rhodamine retained in each section. Most of the spray droplets were deposited onto the anterior region of the model, but sprays with small plume angles were capable of reaching the turbinate region with deposition efficiencies approaching 90%. Minimal dependence on droplet size, viscosity, or device was observed. Changes in inspiratory flow rate (0-60 L/min) had no significant effect on turbinate deposition efficiency. Both plume angle and administration angle were found to be important factors in determining deposition efficiency. For administration angles of 40 degrees or 50 degrees , maximal turbinate deposition efficiency (30-50%) occurred with plume angles of 55-65 degrees , whereas a 30 degrees administration angle gave an approximately 75% deposition efficiency for similar plume angles. Deposition efficiencies of approximately 90% could be achieved with plume angles <30 degrees using 30 degrees administration angles. Both the plume angle and administration angle are critical factors in determining deposition efficiency, while many other spray parameters, including particle size, have relatively minor influences on deposition within the nasal cavity.

Effect of Race on Fine Particle Deposition for Oral and Nasal Breathing

Nasal efficiency for removing fine particles from inhaled air may be affected by variations in nasal structure associated with race. In 11 African American and 11 Caucasian adults (age 18–31 yr) we measured the fractional deposition (DF) of fine particles (1 and 2 μm mass median aerodynamic diameter) (MMAD) for oral and nasal breathing using individual breathing patterns previously measured by respiratory inductance plethysmography during a graded exercise protocol. DF for both nasal and mouth breathing was measured separately by laser photometry at the same tidal volume and breathing rate for resting and light exercise (20% of maximum work load) conditions. From these DF measures, nasal deposition efficiency (NDE) was calculated for each condition. For light exercise conditions, NDE for both 1- and 2-μm particles was less in African Americans versus Caucasians, 0.15 ± 0.07 (SD) versus 0.24 ± 0.11 for 1-μm particles (p = .03), and 0.29 ± 0.13 versus 0.44 ± 0.11 for 2-μm particles (p = .006). The racial differences in NDE were associated with racial differences in nasal resistance and nostril shape. These race-dependent nasal efficiencies are dosimetric factors that should be considered in modeling and assessing particulate dose from human exposure to air pollutants.

Nasal and Lung Deposition of Fine and Coarse Particles in Rats

Deposition of particles in rat airways was measured using two methods. In method 1, a controlled flow of monodisperse particles was passed directly through the nasal airways of an anesthetized rat and nasal deposition efficiency was determined for particles with aerodynamic diameters between 0.5 and 4 μm. In method 2, upper respiratory tract (URT) and lung deposition fractions for unanesthetized rats exposed to radiolabeled particles in head-only units and anesthetized rats exposed in whole-body units were determined for particles with aerodynamic diameters between 0.9 and 3 μm. Animal breathing parameters were measured for method 2 exposures. Nasal deposition efficiency was greater for pulsatile flows than steady state (method 1). Nasal deposition was distinctly higher for method 1 exposures than those using method 2 because particles were 100% inhalable in method 1 and <100% inhalable in the head-only and whole body exposures of method 2. Similarly, deposition was greater in head-only than wholebody exposures because particle inhalability was greater in head-only exposures.

Predicted Nasal and Tracheobronchial Particle Deposition Efficiencies for the Mouse

ii) An11. 0<<'11p. HJy .• Vol. 38. Supplemcn1 I. pp. JJ S-141 . 1994 El ~'· ier Science Ltd Copyrigh1 i ' 1994 British <Xcupa1iona l Hygiene Sociely Printed in Great Britain. All rights reserved 0003-4878/ 94 S7.00 + 0.00 /11/Jaled Particles VII Pergamon PREDICTED NASAL AND TRACHEOBRONCHIAL PARTICLE DEPOSITION EFFICIENCIES FOR THE MOUSE* M. J. OLDHAM, R. F . PHALEN, G. M. SCHUM and D. s. DANIELS Department of Community and Environmental Medicine, University of California, Irvine, CA 92717, U .S.A. Abstract-Few models are available for predicting the efficiency of deposition of-inhaled particles in the various regions of the respiratory tract of the mouse. The purpose of this study was to improve the ability to predict upper airway (nose, pharynx and larynx) and tracheobronchial deposition efficiencies for inhaled aerosols in the laboratory mouse. Currently-used equations for predicting nasal deposition efficiencies in humans are semi-empirical and utilize airflow and/or pressure drop data. Therefore, we measured nasal pressure drop and airflow in anaesthetized mice and used this information, together with published data , to formulate aerosol deposition equations. Tracheobron- chial deposition efficiency is usually predicted by considering three mechanisms (impaction, sedimentation and diffus ion ), along with airway anatomical and airflow information. A typical path tracheobronchial airway geometry, complete to the terminal bronchiole, was developed for the mouse from detailed measurements of three replica respiratory tract casts. Particle deposition efficiency calculations were then performed for the tracheobronchial region of the adult mouse a nd compared with published estimates of aerosol deposition in mice. The calculations, which covered a particle diameter range of 0.1- 100 11m (aerodynamic), tended to underestimate the experimental measure- ments in mice. The calculations did not take into account deposition during exhalation, or the effects of several other complex factors. INTRODUCTION BECAUSE the laboratory mouse has been used extensively to study the effects of inhaled substances, the methods of performing inhalation studies are well developed, and a large database on biological effects under a wide variety of conditions exists, it is important to understand the relationship between exposure dose and target tissue dose. However, mathematical equations that use exposure aerosol characteristics in order to predict doses delivered to specific target tissues are not available. Predicted particle deposition efficiency calculations in the mouse have been constrained by the lack of reliable information on upper airways and on the structure of the tracheobronchial tree. We addressed this problem by making upper airway pressure drop vs. airflow measurements and by performing measurements of tracheobronchial airway dimensions for B6C3F 1 mice. The measured resting pressure drop was used .with experimental data from RAABE et al. (1988) to propose upper respiratory tract deposition efficiency equations. The measured geometry was input into a computer program that used particle deposition equations and airflow rates to obtain calculated particle deposition efficiencies. Nasal deposition efficiency (N,rr) has been predicted for humans by an equation of the form: *This paper was included in Poster Session 2 and the discussion included in the summary presented in Section 12.

Empirical Equations for Nasal Deposition of Inhaled Particles in Small Laboratory Animals and Humans

Based upon available experimental data, a set of empirical equations was derived for nasal deposition efficiency of inhaled particles in the inertial deposition range for four small laboratory animal species: the mouse, hamster, rat, and guinea pig. An equation for nasal deposition in humans was also derived in the same mathematical form to facilitate interspecies comparison. In these equations, deposition efficiency was expressed as a function of particle inertia d2 a Q where da is the particle aerodynamic diameter and Q is the flow rate. Results from the empirical equations showed that nasal deposition was species dependent, and that at the same d2 a Q, species with smaller body weight had higher deposition efficiency. By incorporating the anatomical data of the nasal passage, the deposition equations were rewritten as a function of the product of Stokes number and the total bend angle in nasopharynx. Interspecies deposition differences were found to be greatly reduced in terms of the new variable.

Mucus protection and airway peroxidation following nitrogen dioxide exposure in the rat.

In the current study, biochemical measures of lipid peroxidation following 4-h inhalation exposure to 76 mg/m3 (40 ppm) nitrogen dioxide were correlated with measures of deposition and tissue antioxidant levels in the nasal cavity and the trachea of the Fischer rat. In addition, respiratory-tract mucus samples were collected via esophageal cannulation and nasopharyngeal lavage over known time periods, and were analyzed for phospholipid (PL) content to provide an index of the unsaturated lipids (UL) that they may contain. UL are thought to be important in the scavenging of oxidants by the mucous lining layer. Nasal deposition efficiency, as measured in the surgically isolated upper respiratory tract under unidirectional flow conditions, averaged 25%, corresponding to an absolute deposition rate of 41 nmol/min. Vitamin E levels averaged 1.7, 5.9, and 0.7 nmol/mumol PL in nasal, tracheal, and pulmonary tissues, respectively. The level in the trachea was significantly (p less than 0.005) higher than in the other tissues. As estimated from the increase in lavage PL content over 1 h, the overall mucous PL transport rate was less than 0.013 nmol/min, suggesting the PL of the mucous lining layer could not offer significant protection against the inhaled NO2. Conjugated dienes were detected in two of four pooled nasal tissue samples. Thiobarbituric acid-reactive material levels in tracheal tissues were significantly elevated over control levels by NO2 (p less than 0.05). Thus, despite the relatively high vitamin E levels, 4-h NO2 exposure appeared to result in lipid peroxidation in the trachea and, perhaps, in the nasal airways of the rat, a result that correlated with the apparent lack of oxidant-scavenging species in the mucus lining these airways.