Aerosol Drug Research Articles

Effect of non-spherical shape of dry powder aerosol drugs on their airway deposition distribution.

In the majority of aerosol drug deposition modelling efforts, the particles are approximated by regular spheres. However, microscope images acquired after drug formulation available in the open literature suggest that their shape is not regular in most cases. This work aimed to combine experimental measurements and numerical simulations to reveal the shape factors of the particles of commercialized aerosol drugs and the effect of non-sphericity on the lung deposition distribution of these drugs. Aerosol particles of Bretaris® Genuair®, Buventol® Easyhaler® and Trelegy® Ellipta® were collected on the stages of a Next Generation Impactor after their emission from the dry powder inhalers. The samples were analyzed using scanning electron microscopy techniques. Aspect ratios and dynamic shape factors characteristic of particles in the size fractions representing each impactor stage were determined. Computer modelling of their airway deposition was performed by both neglecting and considering their irregular shape. The results of particle size measurements revealed that there was no size-specific shape factor of the particles, as they could be well characterized by a global shape factor. Although there was some inter-drug difference in terms of shape factors, the values were quite close to unity (usually between 1.02 and 1.06), except for the fiber-shaped particles representing a minority in the composition of Trelegy® Ellipta®, which could be characterized by shape factors of around 1.6. The results of computer simulations of deposition distribution indicate that neglecting the irregular shape does not lead to a major distortion of the simulation results unless fiber-shaped particles are also present after the formulation.

The (re)emergence of aerosol delivery: Treatment of pulmonary diseases and its clinical challenges.

Aerosol delivery represents a rapid and non-invasive way to directly reach the lungs while escaping the hepatic first-pass effect. The development of pulmonary drugs for respiratory diseases such as cystic fibrosis, lung infections, pulmonary fibrosis or lung cancer requires an enhanced understanding of the relationships between the natural physiology of the respiratory system and the pathophysiology of these conditions. This knowledge is crucial to better predict and thereby control drug deposition. Moreover, aerosol administration faces several challenges, including the pulmonary tract, immune system, mucociliary clearance, the presence of fluid on the airway surfaces, and, in some cases, bacterial colonisation. Each of them directly influences on the bioavailability of the active molecule. In addition to these challenges, particle size and the device used to administer the treatment are critical factors that can significantly impact the biodistribution of the drugs. Nanoparticles are very promising in the development of new formulations for aerosol drug delivery, as they can be fine-tuned to reach the entire pulmonary tract and overcome the difficulties encountered along the way. However, to properly assess drug delivery, preclinical studies need to be more thorough to efficiently enhance drug delivery.

Breath and Beyond: Advances in Nanomedicine for Oral and Intranasal Aerosol Drug Delivery.

Designing and standardizing drug formulations are crucial for ensuring the safety and efficacy of medications. Nanomedicine utilizes nano drug delivery systems and advanced nanodevices to address numerous critical medical challenges. Currently, oral and intranasal aerosol drug delivery (OIADD) is the primary method for treating respiratory diseases worldwide. With advancements in disease understanding and the development of aerosolized nano drug delivery systems, the application of OIADD has exceeded its traditional boundaries, demonstrating significant potential in the treatment of non-respiratory conditions as well. This study provides a comprehensive overview of the applications of oral and intranasal aerosol formulations in disease treatment. It examines the key challenges limiting the development of nanomedicines in drug delivery systems, formulation processes, and aerosol devices and explores the latest advancements in these areas. This review aims to offer valuable insights to researchers involved in the development of aerosol delivery platforms.

Particularities of deposition of two ICS-LABA fixed dose combination dry powder aerosol drugs in the airways of COPD patients.

The aim of this study was to analyse the effect of breathing parameters, age, gender and disease status on the lung doses of the two ICS+LABA fixed combination dry powder drugs. Breathing parameters of 113 COPD patients were measured while inhaling through emptied NEXThaler® and Ellipta® inhalers and the corresponding lung doses were calculated. Lung dose of Foster® NEXThaler® was superior to the lung dose of Relvar® Ellipta® in around 85% of the patients. The average value of the ratio of bronchiolar to bronchial deposition fractions was 5.0 for Foster® NEXThaler® and 2.6 for Relvar® Ellipta®. Lung dose was sensitive to the inhalation parameters, such as peak inhalation flow, inhaled volume and breath-hold time. For both studied drugs the dose to the lungs was relatively high for moderate PIF values, but it declined for low (< 35 L/min) and high (> 95 L/min) PIFs. The lung dose increased by the increase of the inhaled volume, but saturated over 1.0 L of inhaled air. Longer breath-hold time led to higher lung deposition, but the dependence was drug-specific. FEV1(%) and FEV1/FVC (%) did not influence the lung dose significantly (p=0.05). Exacerbating patients had lower lung doses (28.8±5.8% for Foster® NEXThaler® and 23.7±3.8% for Relvar® Ellipta®) than their non-exacerbating counterparts (33.7±6.1% for Foster® NEXThaler® and for 24.9±3.9% for Relvar® Ellipta®). The exact clinical consequences of the differences between the deposition distributions of the two drugs could be assessed only by systematic clinical trials.

Droplet deposition dynamics in a realistic three-dimensionally printed human upper airway: An in vitro study

This study presents the first known successful in vitro measurement of both deposition fractions (DFs) and spatial deposition patterns of nebulized droplets in a realistic human upper respiratory tract model. The model, based on computed tomography scan data of a healthy adult male, accurately replicates the complex geometries of the oral and pharyngeal regions. Experiments were conducted using three different vibrating mesh nebulizer (VMN) systems at varying inhalation flow rates (15–60 l/min). Fluorescein-tagged saline solutions were nebulized, with deposition patterns—representing the spatial distribution of deposited droplets—visualized through ultraviolet fluorescence and DFs quantified based on the absorbance of the rinsate solution. Results show that the DFs and patterns are significantly influenced by flow rate, with deposition shifting from the oral cavity to the oropharyngeal region as flow rate increases. This study provides new insight into aerosol transport and deposition in realistic human airways and offers valuable data for optimizing nebulizer design and improving aerosol drug delivery efficiency in clinical applications.

Development of an Inhalable DNA Tetrahedron MicroRNA Sponge.

In designing aerosolized drugs, the challenge lies in achieving optimal penetration and retention. Existing delivery systems prioritize larger particles for prolonged intrapulmonary retention, compromising penetration speed. Conversely, smaller nanoparticles face rapid clearance and limited retention. RNA sponges featuring multiple microRNA binding sites exhibit promising potential for gene expression regulation. However, the complex structure of the frequently utilized cyclic RNA sponge impedes rapid penetration and cellular uptake, restricting its application. This study proposes an innovative approach using a compact tetrahedral framework of nucleic acid to construct an inhalable microRNA sponge. Distinguished by its simplified structure, this microRNA sponge ensures effective microRNA inhibition, rapid tissue penetration, and prolonged residency through prompt endocytosis. Validated in acute lung inflammation models, the approach demonstrates swift restoration of local immune homeostasis. This design addresses the critical need for aerosol vehicles that balance efficient penetration and sustained retention, offering a promising solution for effective gene expression regulation.

The efficacy and safety of aerosol therapy in rhinology

Abstract Aerosol drug administration has a long history as an important part of the treatment for different respiratory disorders in both adult and paediatric patients. The nebulization process permits the drug delivery directly to the upper and lower airways tracts, allowing increased local effectiveness, and avoids systemic side effects. The aerosol therapy is mainly used in pneumology for lower respiratory tract disorders, a series of drugs having a proven efficacy. Few publications present the efficacy and safety of ENT nebulization, despite its worldwide utilization. Topical drug delivery to the nasal cavities and paranasal sinuses via aerosols appears to be an interesting, but also a challenging alternative. The transport and deposition of drugs and aerosol particles into the sinuses is debatable due to several factors: sinuses are poorly perfused and virtually non-ventilated cavities; they are protected by the efficient particle filtration function of the nasal cavities. The review evaluates the efficacy and safety of aerosol therapy in rhinologic pathology.

The effect of bronchoscopic lung volume reduction on the bronchodilator response.

Bronchoscopic lung volume reduction (BLVR) is a method of achieving lung collapse in severely emphysematous regions. One of the measures of success is the improvement in post-bronchodilator forced expiratory volume in the first second (FEV1). The change in bronchodilator response (BDR) following BLVR is typically not reported, however, the changes in lung physiology that accompany endobronchial valve placement may impact aerosol drug delivery and alter the response to bronchodilators. We compared the BDR before and after BLVR to evaluate this effect. We performed a retrospective study to analyze the change in BDR following BLVR. We included patients who underwent pulmonary function test (PFT) within 6 months of BLVR and confirmed complete lobar atelectasis. The pre-BLVR BDR for each patient served as the control, which was then compared to the post-BLVR BDR. The mean difference in the BDR before and after valve placement was determined. The comparison between pre- and post-BLVR means was performed using a t-test. A total of 35 patients were assessed for the study. Fifteen patients were excluded (due to valve removal, incomplete lobar collapse, and no pre- or post-BLVR PFT available). Of the 20 remaining patients, 14 had a positive BDR at baseline before BLVR. Following BLVR, 13 of the 14 patients demonstrated a non-significant increase in the BDR. The mean BDR for pre- and post-valve was 83.6 vs. 116.3 mL, respectively. The mean absolute increase in BDR following BLVR was 32.7 mL [95% confidence interval (CI): -32.5 to 97.8, P=0.31]. When including all 20 patients, the mean BDR pre- and post-BLVR was 47.5 vs. 86.5 mL, respectively, with a mean increase in BDR by 39 mL (95% CI: 22.3 to 100.3, P=0.21). BLVR may improve the BDR in patients with complete lobar atelectasis.

High-precision ultrasonic atomization using oscillating microchannels: Interplay of three-dimensional vibrational modes and droplet ejection mechanisms

Ultrasonic atomization is a critical process for producing micrometer-diameter droplets, widely utilized in aerosol drug delivery, spectrometry, and printing. The geometry of the vessel containing the fluid being atomized and the oscillations of its sidewalls play a crucial role in controlling the wave patterns and hence the droplet ejection process, especially at actuation frequencies exceeding 1 MHz. However, the mechanisms behind droplet ejection under high-frequency ultrasonic actuation remain poorly understood. We employ oscillating high-aspect-ratio Silicon microchannels to create ideal conditions where capillary forces, microchannel geometry, and oscillatory motion work together to precisely confine a liquid film and generate droplets with controlled diameters. We show that the three-dimensional vibrations of the microchannels, particularly the interplay between actuation frequency, amplitude, and channel geometry, can be used to effectively tune the ligament development and droplet breakup. This understanding allows us to establish conditions to reduce actuation power and hence minimize heating, control shear stresses and tune the droplet size on-demand without compromising uniformity and throughput.

The effect of decoupling humidity control on aerosol drug delivery during HFNC for infants.

Aerosol therapy is commonly used during treatment with high-flow nasal cannula (HFNC) in the intensive care unit (ICU). Heated humidification inside the HFNC tubing circuit leads to unwanted condensation, which may greatly limit the efficiency of drug delivery. In this study, we aimed to investigate whether a novel humidification system, which decouples temperature and humidity control, can improve the delivered dose. In a bench study setup, fluorescein sodium solution was nebulized using a vibrating-mesh nebulizer in an infant HFNC circuit to measure the delivered dose, with a conventional versus a novel decoupled humidifier. The deposition of fluorescein inside each breathing circuit component and a final collection filter at the end of the nasal cannula was collected and quantified with a UV-vis spectrometer. Droplet sizes at different sections of the breathing circuit were measured by laser diffraction. Three air flow rates: 5, 10 and 15 L/min, and two nebulizer positions: (1) at the humidifier and (2) after the inspiratory tube, were tested. The delivered dose decreased with increasing flow rate for the conventional setup and was higher when the nebulizer was placed after the inspiratory tube. Turning off the conventional humidifier 10 minutes before and during nebulization did not improve the delivered dose. The decoupled humidifier achieved a significantly higher (p = .002) delivered dose than the conventional setup. The highest delivered dose obtained by the decoupled humidifier was 62.4% when the nebulizer was placed after the humidifier, while the highest dose obtained for the conventional humidifier was 36.3% by placing the nebulizer after the inspiratory tube. In this bench study, we found that the delivered dose for an infant HFNC nebulization setup could be improved significantly by decoupling temperature and humidity control inside the HFNC circuit, as it reduced drug deposition inside the breathing circuit.

Effect of airway wall motion on particle deposition and delivery in the neonatal trachea

Modeling pulmonary drug delivery in the airway using computational fluid dynamics (CFD) simulations tracks drug particles throughout the airway, providing valuable information on the deposition location of inhaled drugs. However, most studies simulate particle transport within static airway models that do not incorporate physiological airway motion; this choice limits accuracy since airway motion directly affects particle transport and deposition, notably in newborns with airway abnormalities such as tracheomalacia. The objective of this study is to determine the effect of airway motion on drug delivery in neonates with and without airway disease. For this study, two control subjects without any airway disease and three subjects with tracheomalacia (dynamic tracheal narrowing) were enrolled. Each subject was imaged at approximately 40-weeks post-menstrual age using magnetic resonance imaging (MRI). MRI data were retrospectively reconstructed to obtain static airway images gated to different time points of the breath (i.e., end expiration and end inspiration) and an image representing combined data from all timepoints (ungated). Virtual airway surfaces (pharynx to main bronchi) were made from each MR image. A moving airway surface was created from surface registration of these surfaces and used as the boundary for a CFD simulation of one inhalation, along with subject-specific inspiratory flow waveforms. To assess the effect of airway wall motion on particle deposition, static-walled simulations, based on the airway surfaces at end inspiration, end expiration, and the ungated airway surface, were also performed using the same flow boundary conditions. Particle transport (particles diameter range 0.5–15 μm) was compared between the simulations during the inhalation. Airway surface motion affected particle transport into the small airways by 65% on average (0.5–5 μm– 22%, 5-15 μm– 86%) compared to static-walled simulations, while comparison between static end expiration and other static-walled simulations using geometries acquired during different phases of breathing differed by more than 500% on average (0.5–5 μm– 45%, 5-15 μm– 741%). For particle deposition, airway surface motion affected by 43% on average (0.5–5 μm– 86%, 5-15 μm– 21%) compared to static-walled simulations and comparison between static end expiration and other static-walled simulations differed by 47% on average (0.5–5 μm– 58%, 5-15 μm– 41%). Differences between dynamic and static deposition results and between static simulations from different timepoints occurred in patients with and without airway disease. This study suggests the importance of using airway wall motion in CFD simulations to model aerosolized drug delivery in the airway. If a CFD simulation is limited to only a static airway image without physiological motion, particle deposition mapping may yield markedly inaccurate results, potentially resulting in higher or lower drug dosing than intended.

Changes in Peak Inspiratory Flow After Acute Bronchodilation: An Observational Study of Patients with Stable Chronic Obstructive Pulmonary Disease.

Introduction: Identifying factors influencing peak inspiratory flow (PIF) is essential for aerosol drug delivery in stable patients with chronic obstructive pulmonary disease. While a minimum PIF for dry powder inhalers (DPIs) is established, acute bronchodilator (BD) effects on PIF remain unknown. Materials and Methods: An inspiratory flow meter (In-Check™ DIAL) was used to measure PIF in stable patients during a 24-week observational cross-sectional study. Additionally, bronchodilator responsiveness (BDR) was determined using the In-Check DIAL device and spirometry. Patients received four puffs of albuterol, and pre- and post-BD PIF, forced expiratory volume in one second (FEV1), and forced vital capacity were measured. Sixty-three patients completed acute BDR data collection from July 31, 2019, to November 9, 2021. Primary endpoints were pre- and post-BD spirometry and PIF. Statistical analyses included PIF correlations with FEV1. BD change was assessed according to inhaler resistance and sex (subgroup analysis). Results: Median patient age was 64.8 years, 85.7% were non-Hispanic White, and 57.1% were female. The median increase in absolute PIF (In-Check DIAL) was 5.0 L/min, and the % PIF change was 8.9%. With albuterol, 57.1% experienced a PIF BD change >5.0%, whereas 49.2% experienced a change >10.0%. Similarly, 55.6% experienced an FEV1 BD change >5.0% and 28.6% had a >10.0% FEV1 BD change with albuterol. PIF was weakly correlated with FEV1 BD change (absolute; % PIF; r = 0.28 [p = 0.02]; r = 0.21 [p = 0.11]). Pre- and post-BD median PIF were 75.5 and 83.5 L/min for low-to-medium-resistance DPI and 45.0 and 52.0 L/min for high-resistance, respectively. The median increases in pre- and post-BD PIF were 9.0 L/min in males and 4.5 L/min in females. In contrast to when using the In-Check DIAL device, we observed no consistent bronchodilatory effects on PIF measured by spirometry. Conclusions: Using the In-Check DIAL device, ∼50% of patients experienced >10% PIF increase after acute BD, potentially enhancing medication lung deposition. Further research is required to understand PIF's impact on medication delivery. ClinicalTrials.gov Identifier: NCT04168775.

High-flow nasal cannula and in-line aerosolised bronchodilator delivery during severe exacerbation of asthma in adults: a feasibility observational study

BackgroundAsthma is a common chronic respiratory disease affecting 1–29% of the population in different countries. Exacerbations represent a change in symptoms and lung function from the patient's usual condition that requires emergency department (ED) admission. Recently, the use of a High-Flow Nasal Cannula (HFNC) plus an in-line vibrating mesh nebulizer (VMN) for aerosol drug delivery has been advocated in clinical practice. Thus, this pilot observational study aims to investigate the feasibility of HFNC treatment with VMN for in-line bronchodilator delivery in patients with severe asthma. MethodsThis study was conducted from May 2022 to May 2023. Subjects ≥18 years old with a previous diagnosis of asthma who were admitted to the ED during severe exacerbation were included. The primary endpoint was the change in peak expiratory flow ratio (PEFR) after 2-h of treatment with bronchodilator delivered by HFNC with in-line VMN. Additional outcomes were changes in forced expiratory volume in 1 s (FEV1) and clinical variables before treatment. Results30 patients, mean age of 43 (SD ± 16) years, mostly female (67%) were studied. A significant change in PEFR (147 ± 31 L/m vs. 220 ± 38 L/m; p < 0.001) was observed after treatment with HFNC and in-line VMN with significant improvement in clinical variables. And no subjects required invasive mechanical ventilation (IMV) during the study. ConclusionsHFNC treatment with in-line VMN for bronchodilator delivery appears feasible and safe for patients with severe asthma exacerbation. These preliminary promising results should be confirmed with appropriately large-designed studies.

Use of process intensification concepts for targeted delivery of inhaled aerosolized medicines

Process intensification (PI) concepts have potential applications beyond the classic industrial problems solved by chemical engineering. This paper discusses the flow and mass transfer intensification using acoustic waves to enhance drug delivery to the nasal cavity. The efficiency of drug delivery to the nose still needs improvement, and the mechanisms related to using acoustic waves to increase it have yet to be studied. The influence of pressure pulsations induced by an acoustic wave (∼100 Hz) on the concentration, droplet size, and flow structure of the mists delivered from medical nebulizers was studied. The direct visualization showed that pulsations intensify aerosol deposition inside narrow channels due to particle displacement perpendicularly to the main flow direction. This motion also allows for particle penetration via narrow openings. UV-assisted observation of the intensified aerosol deposition inside the anatomical cast of the nasal cavity confirmed the importance of acoustic pulsations for intranasal drug delivery, also helping aerosol penetrate hard-to-reach areas (including the paranasal sinuses). A new idea regarding appropriate time control of acoustic pulsations has been proposed to improve the aerosol drug mass transfer in the nose. The study shows that PI has great potential to expand into new and interdisciplinary areas.

A Technique to Generate and Deliver Drug Aerosols Directly to Mouse Lungs

A Technique to Generate and Deliver Drug Aerosols Directly to Mouse Lungs

A Technique to Generate and Deliver Drug Aerosols Directly to Mouse Lungs

A Technique to Generate and Deliver Drug Aerosols Directly to Mouse Lungs

Aerosol drug therapy in critically ill patients (Aero-in-ICU study): A multicentre prospective observational cohort study.

In recent years, a significant understanding of delivering optimal aerosol therapy and the availability of various drugs and devices have led to an increase in its use in clinical practice. There are only a few studies available regarding their use in critically ill patients from a few parts of the world. We aimed to study the practice pattern of aerosol therapy in critically ill patients from Indian intensive care units (ICUs). After ethical approval, this multi-centric prospective observational study was performed over a study period of four weeks. Newly admitted adult patients considered who had an artificial airway and/or ventilation (including non-invasive). Patients were followed up for the next 14 days or until ICU discharge/death (whichever came first) for details of each aerosol therapy, including ongoing respiratory support, drug type, and aerosol-generating device. From the nine participating centers across India, 218 patients were enrolled. Of 218 enrolled patients, 72.48% received 4884 aerosols with 30.91 ± 27.15 (95%CI: 26.6-35.1) aerosols per patient over 1108 patient days. Approximately 62.7% during IMV, 30.2% during NIV, 2.3% in spontaneously breathing patients with an artificial airway during weaning, and 4.7% were given without an artificial airway after weaning or decannulation. In 59%, a single drug was used, and bronchodilators were the most frequent. The jet nebulizer was the most common, followed by the ultrasonic and vibrating mesh aerosol generator. The ventilator setting was changed in only 6.6% of the aerosol sessions with IMV and none with NIV. Aerosol therapy is frequently used with a wide variation in practices; bronchodilators are the most commonly used drugs, and jet nebulizers are the most widely used.

Effects of the deformation and size of the upper airway on the deposition of aerosols

Aerosol drug delivery in the human airway is significantly affected by the morphology and size of the airway. This work developed a CFD-DEM model to simulate and analyze air flow and powder dynamics in combined inhaler-airway systems with different degrees of airway deformation (non-deformed, 50%, and 75% deformed) and sizes (adult, 0.80, and 0.62 scaled). The airways were generated based on a regular airway constructed from the MRI images through finite element method (for deformed airways) or scaling-down (for smaller airways). The airways were connected to Turbuhaler® through a connector. The results showed that under the same flow rate, the variation in the airway geometry and size had a minimum impact on the flow field and powder deposition in the device and the connector. However, deformation caused more particle deposition in the deformed region. Notably, the airway with 50% deformation had the most particles passing through the airway with the largest particle sizes due to its lower air velocity in the deformed area. Reducing airway size resulted in more powder deposition on the airway, particularly at the pharynx and mouth regions. This was because, with the same flow rate, the flow velocity in the smaller airway was higher, causing more particle–wall collisions in the mouth and pharynx regions. More importantly, the deposition efficiency in the 0.62-scaled airway was significantly higher than the other two airways, highlighting the importance of the different administration of aerosol drugs for young children.

The Effect of Priming new Plastic Spacers with 20 Puffs Salbutamol on Bronchodilator Response in Asthmatic Children.

The static charge on the plastic body of spacers attracts drug aerosols, reducing the drug available for inhalation from plastic spacers. Some instructions exist to decrease the electric charge on plastic spacers, such as priming them with salbutamol (20 puffs) before use. This study investigates whether priming plastic spacer devices with this method can improve the bronchodilator test result. This study included children with stable mild to moderate asthma. All subjects underwent two pulmonary function tests to evaluate their bronchodilator response on separate days at 24-48 hours intervals. On each day, spirometry was performed at the baseline and 15 min after inhalation of four puffs of salbutamol (100 μg/puff) through either a primed or a new spacer. The change in forced expiratory volumein the first second (FEV1) after inhaling salbutamol was the primary outcome measure. When the patients used a new spacer, the mean baseline FEV1 (% predicted) and FEV1/FVC (forced vital capacity) were 89.56±11.95 and 86.17±6.87, respectively. However, the mean increase in FEV1 from the baseline was 10.87±8.99 in this group. On the other hand, with the primed spacer, the respective mean baseline FEV1 and FEV1/FVC values were 89.41±12.14 and 85.49±6.76, while it increased by 12.1±11.01 after salbutamol inhalation. There were no significant differences between the techniques regarding the variation in FEV1 before and after bronchodilator use via a new spacer or primed spacer. Priming new plastic spacers with 20 puffs of salbutamol did not cause additional bronchodilation in asthmatic children, suggesting this practice is inefficient in clinics.

The Effects of Inspiratory Flows, Inspiratory Pause, and Suction Catheter on Aerosol Drug Delivery with Vibrating Mesh Nebulizers During Mechanical Ventilation.

Background: Some experts recommend specific ventilator settings during nebulization for mechanically ventilated patients, such as inspiratory pause, high inspiratory to expiratory ratio, and so on. However, it is unclear whether those settings improve aerosol delivery. Thus, we aimed to evaluate the impact of ventilator settings on aerosol delivery during mechanical ventilation (MV). Methods: Salbutamol (5.0 mg/2.5 mL) was nebulized by a vibrating mesh nebulizer (VMN) in an adult MV model. VMN was placed at the inlet of humidifier and 15 cm away from the Y-piece of the inspiratory limb. Eight scenarios with different ventilator settings were compared with endotracheal tube (ETT) connecting 15 cm from the Y-piece, including tidal volumes of 6-8 mL/kg, respiratory rates of 12-20 breaths/min, inspiratory time of 1.0-2.5 seconds, inspiratory pause of 0-0.3 seconds, and bias flow of 3.5 L/min. In-line suction catheter was utilized in two scenarios. Delivered drug distal to the ETT was collected by a filter, and drug was assayed by an ultraviolet spectrophotometry (276 nm). Results: Compared to the use of inspiratory pause, the inhaled dose without inspiratory pause was either higher or similar across all ventilation settings. Inhaled dose was negatively correlated with inspiratory flow with VMN placed at 15 cm away from the Y-piece (rs = -0.68, p < 0.001) and at the inlet of humidifier (rs = -0.83, p < 0.001). The utilization of in-line suction catheter reduced inhaled dose, regardless of the ventilator settings and nebulizer placements. Conclusions: When VMN was placed at the inlet of humidifier, directly connecting the Y-piece to ETT without a suction catheter improved aerosol delivery. In this configuration, the inhaled dose increased as the inspiratory flow decreased, inspiratory pause had either no or a negative impact on aerosol delivery. The inhaled dose was greater with VMN placed at the inlet of humidifier than 15 cm away the Y-piece.