Vibrating Mesh Nebulizer Research Articles

177 Aerosol Delivery Evaluation of a Vibrating Mesh Nebulizer and a Jet Nebulizer During Breath Actuated and Continuous Nebulization Modes in Spontaneously Breathing Adult and Pediatric Models

177 Aerosol Delivery Evaluation of a Vibrating Mesh Nebulizer and a Jet Nebulizer During Breath Actuated and Continuous Nebulization Modes in Spontaneously Breathing Adult and Pediatric Models

Physiologic Effects of Instilled and Aerosolized Surfactant Using a Breath-Synchronized Nebulizer on Surfactant-Deficient Rabbits.

Surfactant administration incorporates liquid bolus instillation via endotracheal tube catheter and use of a mechanical ventilator. Aerosolized surfactant has generated interest and conflicting data related to dose requirements and efficacy. We hypothesized that aerosolized surfactant with a novel breath-actuated vibrating mesh nebulizer would have similar efficacy and safety as instilled surfactant. Juvenile rabbits (1.50 ± 0.20 kg, n = 17) were sedated, anesthetized, intubated, and surfactant was depleted via lung lavage on mechanical ventilation. Subjects were randomized to receive standard dose liquid instillation via catheter (n = 5); low dose surfactant (n = 5) and standard dose surfactant (n = 5) via aerosol; and descriptive controls (no treatment, n = 2). Peridosing events, disease severity and gas exchange, were recorded every 30 min for 3 h following surfactant administration. Direct-Instillation group had higher incidence for peridosing events than aerosol. Standard dose liquid and aerosol groups had greater PaO2 from pre-treatment baseline following surfactant (p < 0.05) with greater ventilation efficiency with aerosol (p < 0.05). Our study showed similar improvement in oxygenation response with greater ventilation efficiency with aerosol than liquid bolus administration at the same dose with fewer peridosing events. Breath-synchronized aerosol via nebulizer has potential as a safe, effective, and economical alternative to bolus liquid surfactant instillation.

Evaluation of Aerosol Drug Delivery Options during Adult Mechanical Ventilation in the COVID-19 Era.

Drug delivery devices used for aerosol therapy during mechanical ventilation to ease the symptoms of respiratory diseases provide beneficial treatment but can also pose challenges. Reflecting the significant changes in global guidance around aerosol usage and lung-protective ventilation strategies, seen in response to the COVID-19 pandemic, for the first time, we describe the drug delivery performance of commonly used devices under these conditions. Here, vibrating mesh nebuliser (VMN), jet nebuliser (JN) and pressurised metered-dose inhaler (pMDI) performance was assessed during simulated adult mechanical ventilation. Both standard test breathing patterns and those representatives of low tidal volume (LTV) ventilation with concurrent active and passive humidification were investigated. Drug delivery using a VMN was significantly greater than that with a JN and pMDI for both standard and LTV ventilation. Humidification type did not affect the delivered dose across all device types for standard ventilation. Significant variability in the pMDI dosing was evident, depending on the timing of actuation and the adapter type used. pMDI actuation synchronised with inspiration resulted in a higher delivered drug dose. The type of adapter used for pMDI actuation influenced drug delivery, with the highest dose observed using the CombiHaler.

Effect of Vibrating Mesh Nebulizer Aerosol Technology on the In Vitro Activity of Ribavirin Against Respiratory Syncytial Virus.

Ribavirin is an antiviral drug that for many years has been administered to the lungs by aerosolization. Despite advancements in oral delivery routes, there has been a renewed interested in delivering ribavirin via the pulmonary system in select patients and the severely ill. The vibrating mesh nebulizer was previously demonstrated to be an effective alternative to the small-particle aerosol generator in particle size, chemical makeup, and concentrations of the ribavirin before and after nebulization. However, the antiviral activity of ribavirin has never been examined. We sought to study ribavirin's activity before and after nebulization via vibrating mesh nebulizer. We grew and infected human epithelial type 2 cells and primary airway epithelial cells with respiratory syncytial virus (RSV). We then compared the antiviral effect of non-nebulized (control) and aerosolized ribavirin to untreated controls. We used traditional plaque assay and real-time polymerase chain reaction to determine the quantity of virus. Both non-nebulized (control) and nebulized ribavirin reduced the size of RSV plaques compared to untreated controls. Additionally, the non-nebulized and nebulized ribavirin equally inhibited RSV replication. There were no statistically significant differences between the non-nebulized and nebulized ribavirin across all time points. The vibrating mesh nebulizer did not affect the antiviral properties of nebulized ribavirin when compared to non-nebulized drug. Our findings add supporting evidence for the use of the vibrating mesh nebulizer in the administration of inhaled ribavirin.

Aerosol delivery of inhalation devices with different add-on connections to invasively ventilated COPD subjects: An in-vivo study

Aerosol delivery to mechanically ventilated patients requires add-on connections to place the inhalation device within the ventilation circuit. The study aimed to evaluate the performance of Combihaler in dual limb invasive mechanical ventilation (IMV).A ventilator with a humidified dual limb circuit was adjusted to volume-controlled mode to imitate the adult breathing parameters. 24 (12 females) intubated chronic obstructive pulmonary disease (COPD) subjects had undergone the study. All patients were prescribed inhaled salbutamol dose delivered by either a metered-dose inhaler (pMDI) or vibrating mesh nebulizer (VMN). Each subject received salbutamol in four different inhalation device/connection conditions; pMDI+VMN+Combihaler, VMN+Combihaler, VMN+T-piece, and pMDI+T-piece. They were individually placed in the inspiratory limb at Y-piece. 5mg salbutamol was delivered by VMN with and without 2 pMDI puffs of salbutamol (100 µg), and 500µg was delivered by pMDI+T-piece. After aerosol delivery, two urine samples were collected from the patient; 30 min post-inhalation (USAL0.5) and cumulatively 24 h post-inhalation (USAL24) as indexes of lung deposition and systemic absorption, respectively. For the ex-vivo study, a collecting filter was placed before an endotracheal tube (ETT) to collect the delivered inhalable dose. In-vitro aerodynamic characteristics were also investigated.pMDI+VMN+Combihaler delivered more salbutamol to the lung and the ex-vivo filter than VMN+T-piece (p˂0.05, p≤0.01, respectively). VMN delivered a higher salbutamol amount to the lung, systemically, and the ex-vivo filter than pMDI+T-piece (p˂0.001). pMDI+VMN+Combihaler and VMN+Combihaler delivered aerosols with a less mass median aerodynamic diameter (MMAD) and higher fine particle fraction (FPF) compared to VMN+T-piece (p≤0.01 for MMAD, p˂0.01 for FPF) and pMDI+T-piece (p˂0.01 for both MMAD and FPF).Results of the study showed that pMDI+VMN+ Combihaler delivered more salbutamol than VMN+T-piece in IMV and demonstrate that 5 puffs (500-µg) of salbutamol with pMDI+T-piece has a lower aerosol delivering power at the level of USAL0.5, USAL24, and the ex-vivo inhalable dose than 5 mg nebulized salbutamol by VMNs in IMV.

Impact of phospholipids, surfactants and cholesterol selection on the performance of transfersomes vesicles using medical nebulizers for pulmonary drug delivery

The aim of this study is to formulate and optimize novel transfersome formulations for pulmonary drug delivery. Transfersome formulations (F1 – F18) were prepared by a thin-film method using three phospholipids (Soya phosphatidylcholine (SPC), Dimyristoly phosphatidylcholine (DMPC) and Hydrogenated soya phosphatidylcholine (HSPC)), in combination with three different surfactants (Tween 80, Span 80 and Span 20) with or without cholesterol, employing Beclomethasone dipropionate (BDP) as the model drug. Nano-transfersome formulations post-extrusion were delivered to a Two-stage Impinger (TSI) via three medical nebulizers (i.e. Air-jet, Ultrasonic and Vibrating mesh nebulizer). Based on the physicochemical properties, formulations F1 (SPC and Tween 80), F7 (DMPC and Tween 80) and F13 (HSPC and Tween 80) demonstrated significantly smaller VMD (162.34 ± 6.48, 198.66 ± 6.64, and 183.52 ± 7.34 nm), and significantly higher entrapment efficiency (97.56 ± 2.45, 95.67 ± 4.26 and 95.06 ± 3.38%). Based on nebulization performance, the Ultrasonic nebulizer exhibited the shortest nebulization time for formulations F1, F7 and F13 (i.e. 17.88 ± 2.45, 19.26 ± 2.04 and 19.59 ± 2.12 min), and higher output rate (212.04 ± 11.54, 194.61 ± 10.27 and 192.43 ± 9.84 mg/min), when compared to Air-jet and Vibrating mesh nebulizers. Irrespective of nebulizer type, significantly higher BDP deposition was observed in the lower stage of TSI for the F1 formulation (on average of 61%), whereas a higher amount of BDP was deposited in the upper stage of TSI using the F7 formulations (49%). Moreover, Formulation F1 in combination with Air-jet nebulizer demonstrated higher emitted dose (ED) and fine particle fraction (FPF) (82% and 83%), when compared to the counterpart formulations and nebulizer types investigated. This study has demonstrated that based on nebulizer performance, BDP deposition and formulation type; the F1 formulation in combination with an Air-jet nebulizer is most optimal for lower respiratory tract deposition, whereas the F7 formulation in combination with an Ultrasonic nebulizer is ideal for upper respiratory tract deposition.

Aerosol Delivery via Continuous High-Frequency Oscillation During Mechanical Ventilation.

As the use of continuous high-frequency oscillation combined with nebulization during mechanical ventilation becomes more prevalent clinically, it is important to evaluate its aerosol delivery efficacy. A bench study was conducted that simulated 2 adult and 2 pediatric conditions. A continuous high-frequency oscillation device integrated into the inspiratory limb of a conventional critical care ventilator was attached to an endotracheal tube (ETT) with a collection filter and test lung. High-frequency oscillation with high-flow setting was used with jet nebulizers attached to the manifold, and a vibrating mesh nebulizer placed between the ETT and the ventilator circuit versus at the inlet of the humidifier. Albuterol (2.5 mg in 3 mL) was nebulized for each condition (no. = 3). The drug was eluted from the collection filter and assayed with ultraviolet spectrophotometry (276 nm). During continuous high-frequency oscillation, the mean inhaled dose with jet nebulizers was low (<2% with the adult settings and <1% with the pediatric settings). Across both adult and pediatric conditions, when the vibrating mesh nebulizer was placed between the ETT and the Y-piece during continuous high-frequency oscillation, the inhaled dose was higher than with the placement of the vibrating mesh nebulizer at the inlet of the humidifier, median 11.1% (IQR 7.0%-13.7%) median 6.0% (IQR 3.9%-7.2%) (P = .002) respectively, but still lower than the inhaled dose with the vibrating mesh nebulizer placed at the inlet of the humidifier with continuous high-frequency oscillation off, median 22.7% (IQR 19.5%-25.4%) versus median 11.1% (IQR 7.0%-13.7%) (P < .001). The inhaled dose with the 10-year-old scenario was higher than with the 5-year-old scenario in all settings except aerosol delivery via continuous high-frequency oscillation. During invasive mechanical ventilation with continuous high-frequency oscillation, aerosol delivery with jet nebulizers in the manifold resulted in a marginal inhaled dose. The vibrating mesh nebulizer at the ETT during continuous high-frequency oscillation delivered 6-fold more aerosol than did the jet nebulizer, while delivering only half of the inhaled dose with the vibrating mesh nebulizer placed at the inlet of the humidifier without continuous high-frequency oscillation.

In-vitro and in-vivo comparisons of high versus low concentrations of inhaled epoprostenol to adult intubated patients

BackgroundInhaled epoprostenol (iEPO) has been shown to reduce pulmonary artery pressure and improve oxygenation. iEPO is mainly delivered via a syringe pump with feed tubing connected to a vibrating mesh nebulizer with high or low formulation concentration delivery.MethodsAn in vitro study and a two-period retrospective case–control study were implemented. The in vitro study compared iEPO delivery via invasive ventilation at low concentrations of 7.5, and 15 mcg/mL and high concentration at 30 mcg/mL, to deliver the ordered dose of 30 and 50 ng/kg/min for three clinical scenarios with predicted body weight of 50, 70 and 90 kg. While in the clinical study, adult patients receiving iEPO via invasive ventilation to treat refractory hypoxemia, pulmonary hypertension, or right ventricular failure were included. 80 patients received low concentration iEPO at multiple concentrations (2.5, 7.5, and 15 mcg/mL, depending on the ordered dose) from 2015 to 2017, while 84 patients received high concentration iEPO at 30 mcg/mL from 2018 to 2019.ResultsIn the in vitro study, there were no significant differences in aerosol deposition between high vs low concentrations of iEPO at a dose of 50 ng/kg/min. In the clinical study, age, gender, ethnicity, and indications for iEPO were similar between high and low concentration groups. After 30–120 min of iEPO administration, both delivery strategies significantly improved oxygenation in hypoxemic patients and reduced mean pulmonary arterial pressure (mPAP) for patients with pulmonary hypertension. However, no significant differences of the incremental changes were found between two delivery groups. Compared to low concentration, high concentration delivery group had better adherence to the iEPO weaning protocol (96% vs 71%, p < 0.001), fewer iEPO syringes utilized per patient (5 [3, 10] vs 12 [6, 22], p = 0.001), and shorter duration of invasive ventilation (6 [3, 12] vs 9 [5, 18] days, p = 0.028). Intensive care unit length of stay and mortality were similar between two groups.ConclusionCompared to low concentration delivery of iEPO, high concentration iEPO via a vibrating mesh nebulizer maintained clinical benefits and increased clinician compliance with an iEPO weaning protocol, required less medication preparation time, and shortened duration of invasive ventilation.

Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19.

The coronavirus disease 2019 (COVID-19) is an unprecedented pandemic that has severely impacted global public health and the economy. Hydroxychloroquine administered orally to COVID-19 patients was ineffective, but its antiviral and anti-inflammatory actions were observed in vitro. The lack of efficacy in vivo could be due to the inefficiency of the oral route in attaining high drug concentration in the lungs. Delivering hydroxychloroquine by inhalation may be a promising alternative for direct targeting with minimal systemic exposure. This paper reports on the characterisation of isotonic, pH-neutral hydroxychloroquine sulphate (HCQS) solutions for nebulisation for COVID-19. They can be prepared, sterilised, and nebulised for testing as an investigational new drug for treating this infection. The 20, 50, and 100 mg/mL HCQS solutions were stable for at least 15 days without refrigeration when stored in darkness. They were atomised from Aerogen Solo Ultra vibrating mesh nebulisers (1 mL of each of the three concentrations and, in addition, 1.5 mL of 100 mg/mL) to form droplets having a median volumetric diameter of 4.3–5.2 µm, with about 50–60% of the aerosol by volume < 5 µm. The aerosol droplet size decreased (from 4.95 to 4.34 µm) with increasing drug concentration (from 20 to 100 mg/mL). As the drug concentration and liquid volume increased, the nebulisation duration increased from 3 to 11 min. The emitted doses ranged from 9.1 to 75.9 mg, depending on the concentration and volume nebulised. The HCQS solutions appear suitable for preclinical and clinical studies for potential COVID-19 treatment.

Effects of Air Purifiers on the Spread of Simulated Respiratory Droplet Nuclei and Virus Aggregates.

The present study was performed to quantitatively evaluate the effects of air purifiers on the spread of COVID-19 and to suggest guidelines for their safe use. To simulate respiratory droplet nuclei and nano-sized virus aggregates, deionized water containing 100 nm of polystyrene latex (PSL) particles was sprayed using a vibrating mesh nebulizer, and the changes in the particle number concentration were measured for various locations of the particle source and air purifier in a standard 30 m3 test chamber. The spread of the simulated respiratory droplet nuclei by the air purifier was not significant, but the nano-sized aggregates were significantly affected by the airflow generated by the air purifier. However, due to the removal of the airborne particles by the HEPA filter contained in the air purifier, continuous operation of the air purifier reduced the number concentration of both the simulated respiratory droplet nuclei and nano-sized aggregates in comparison to the experiment without operation of the air purifier. The effect of the airflow generated by the air purifier on the spread of simulated respiratory droplet nuclei and nano-sized aggregates was negligible when the distance between the air purifier and the nebulizer exceeded 1 m.

A hybrid in vitro in silico framework for albuterol delivery through an adult ventilator circuit to a patient-specific lung airway model

An integrated in vitro in silico approach was employed to investigate albuterol administration to an adult lung airway. Particle size characterization of aerosolized albuterol generated by a jet- and vibrating mesh nebulizer was evaluated in vitro using an adult ventilator circuit that consisted of an endotracheal tube (ETT) connected to a cooled Next Generation Impactor. The aerosol particle size distribution sampled by spectrophotometry was used to predict particle deposition in an in silico patient-specific seven-generation airway model using computational fluid dynamics (CFD). A Lagrangian particle tracking algorithm was used to investigate the effect of nebulizer type and position on drug delivery and compare the efficacy of drug administration through endotracheal intubation and oral route. A vibrating mesh nebulizer produced a larger lung dose than the jet nebulizer, with the aerosol characteristics being dependent on the location of the nebulizer in the ventilator circuit. The CFD analysis showed that the vibrating mesh nebulizer placed at the ventilator had a lower global and local deposition fraction down to the 7th airway generation with higher penetration beyond. Besides, delivery through the ETT was more efficient than oral delivery for the studied conditions. Particle deposition patterns in the various lung lobes were evaluated. Placement of the nebulizer in an adult ventilator circuit could target different areas of the lung.

Effect of functional principle, delivery technique, and connection used on aerosol delivery from different nebulizers: An in-vitro study

ObjectiveNebulizers can be divided according to their functional principle into jet, ultrasonic and vibrating mesh nebulizers with intermittent or continuous aerosol delivery and may be used with many different adapters and connections and all can influence their efficiency. The aim of the present work was to evaluate the effect functional principle, delivery technique, and connection used on aerosol delivered from four different nebulizers. MethodsFour nebulizers were used in the study; three of them were jet nebulizers (JNs; AeroEclipse, NebuTech, En ful Kit) and one of them was Aerogen Solo vibrating mesh nebulizers (VMN). AeroEclipse and NebuTech are intermittent output nebulizers, while the rest are continuous output nebulizers. Aerogen Solo was used with either a standard T-piece or Aerogen Ultra holding chamber, and En ful Kit was used with a standard T-piece or Circulaire II holding chamber. 2 ml of salbutamol was nebulized to determine the total emitted dose (TED) and aerodynamic droplet characteristics of the emitted aerosol from the 6 different sets (4 nebulizers with T-piece and 2 holding chambers). ResultsThe mean ± SD TED from VMN was significantly higher than all the JNs (p < 0.05). Aerogen Ultra with VMN did not show a significant effect on TED compare to T-piece, but it significantly increased (p < 0.05) fine particle dose (FPD; 3091.5 ± 189.4 μg) and fine particle fraction (FPF; 72.7 ± 3.6%). However, the Circulaire II with En ful Kit had significantly higher TED, FPD, and FPF compared to T-piece (p < 0.05). Intermittent JNs (AeroEclipse and NebuTech) had significantly higher TED (p < 0.05) compared to the continuous JNs (En ful Kit) with no significant effect on the other parameters studied. AeroEclipse had the highest MMAD and Aerogen Solo Ultra has the lowest in MMAD. ConclusionsThe functional principle, delivery technique, and connection used had a significant effect on aerosol delivered from nebulizers. VMNs are significantly better than JNs. Intermittent delivery has significantly better TED than continuous delivery. Holding chamber with both VMNs and JNs improved aerosol delivery compared to standard T-piece.

Degradation of lipid based drug delivery formulations during nebulization

Encapsulating pharmaceuticals in protective lipid based nanoparticles, and nebulizing them towards the target area in the body offers a range of clinical advantages. However, the process of nebulization might possibly damage sensitive nanoparticle structures, such as liposomes, resulting in loss of active pharmaceutical ingredients. We compare this loss for two types of lung inhalation devices: high-frequency piezo-actuated vibrating mesh nebulizers and non-actuated continuous jet nebulizers. We find that vibrating mesh nebulizers cause model liposomes to release more than ten times as much encapsulated material as the continuous jet nebulizers because the energies involved in nebulization are much larger. This result highlights the importance of applying a mild nebulization technology when administering shear-sensitive drug formulations such as lipid nanoparticle based drugs to the lungs.

Impact of different nebulisers' connections on aerosol therapy.

Aerosol therapy has the advantage of a higher safety because of the local deposition of inhaled medication to the lung; however, the main drawback is the low and variable amount of delivered drug to patients. Hence, this study aimed to investigate the effect of different accessory connections on aerosol delivery from different nebulisers. This study consisted of 3 main models: in vitro, in vivo and ex vivo models. In vitro model, 6 nebulisers (3 Jet (Dolphin (2030 2001), Philips (SideStream) and Tylenol (TL009002)) and 3 vibrating mesh nebulisers (VMNs) (Aerogen Pro, Solo, an Nivo)) were charged with 5mg/2 mL salbutamol and connected to 2 different connections (T-piece and Circulaire II Hybrid) with an inhalation filter attached to a breathing simulator. Inhaled amounts of drug (inhalation filter) and that remained inside nebuliser were measured. Concerning ex vivo and in vivo models, 24 subjects were involved in the study and they received 5mg/2mL salbutamol from 1 Jet nebuliser and 1 VMNs using both connections. Two urine samples were collected post 30minutes and pooled 24hours urine collection. For the ex vivo model, inhaled amounts of salbutamol were collected on filters placed between the subjects and the nebuliser. Inhaled amounts of salbutamol expressed by the amount of drug detected on inhalation filters (for both in vitro and ex vivo) were significantly higher from both Jet and VMNs connected to the Circulaire II Hybrid connection than that released from nebulisers connected to T-piece. VMNs delivered a higher amount compared with jet nebulisers. The amount released from jet nebulizers were variables, unlike VMNs. Regarding in vivo results, amounts of drug detected in 30minutes urine samples were consistent with in vitro and ex vivo models reflecting higher and significant amounts of drug delivered to the patient's lung for Circulaire II Hybrid connection compared with T-piece regarding both nebulisers. Using a valved chamber with jet and VMNs significantly improved the inhaled amount of the emitted aerosol. VMNs were more effective than jet nebulisers with both connections.

In vitro delivery efficiencies of nebulizers for different breathing patterns

BackgroundNebulizers are medical devices that deliver aerosolized medication directly to lungs to treat a variety of respiratory diseases. However, breathing patterns, respiration rates, airway diameters, and amounts of drugs delivered by nebulizers may be respiratory disease dependent.MethodIn this study, we developed a respiratory simulator consisting of an airway model, an artificial lung, a flow sensor, and an aerosol collecting filter. Various breathing patterns were generated using a linear actuator and an air cylinder. We tested six home nebulizers (jet (2), static (2), and vibrating mesh nebulizers (2)). Nebulizers were evaluated under two conditions, that is, for the duration of nebulization and at a constant output 1.3 mL using four breathing patterns, namely, the breathing pattern specified in ISO 27427:2013, normal adult, asthmatic, and COPD.ResultsOne of the vibrating mesh nebulizers had the highest dose delivery efficiency. The drug delivery efficiencies of nebulizers were found to depend on breathing patterns.ConclusionWe suggest a quantitative drug delivery efficiency evaluation method and calculation parameters that include considerations of constant outputs and residual volumes. The study shows output rates and breathing patterns should be considered when the drug delivery efficiencies of nebulizers are evaluated.

A Safety and Tolerability Study of Thin Film Freeze-Dried Tacrolimus for Local Pulmonary Drug Delivery in Human Subjects.

Due to the low and erratic bioavailability of oral tacrolimus (TAC), the long-term survival rate following lung transplantation remained low compared to other solid organs. TAC was reformulated and developed as inhaled formulations by thin film freezing (TFF). Previous studies reported that inhaled TAC combined with 50% w/w lactose (LAC) was safe and effective for the treatment of lung transplant rejection in rodent models. In this study, we aimed to investigate the safety and tolerability of TFF TAC-LAC in human subjects. The formulation can be delivered to the lung as colloidal dispersions after reconstitution and as a dry powder. Healthy subjects inhaled TAC-LAC colloidal dispersions at 3 mg TAC/dose via a vibrating mesh nebulizer in the first stage of this study and TAC-LAC dry powder at 3 mg TAC/dose via a single dose dry powder inhaler in the second stage. Our results demonstrated that oral inhalation of TAC-LAC colloidal dispersions and dry powder exhibited low systemic absorption. Additionally, they were well-tolerated with no changes in CBC, liver, kidney, and lung functions. Only mild adverse side effects (e.g., cough, throat irritation, distaste) were observed. In summary, pulmonary delivery of TFF TAC-LAC would be a safe and promising therapy for lung transplant recipients.

Influence of liposomes composition on their stability during the nebulization process by vibrating mesh nebulizer

In this study, three different molecules (cholesterol, phosphatidic acid, and polyethylene glycol) were used for the stabilization of liposomes during the nebulization process. The purpose of this article is to answer the question of whether the change in the composition of liposomes affected the parameters of generated aerosol and whether the nebulization process affected observed properties of liposomes. Firstly, liposomes with different composition were prepared and their properties were checked by dynamic and electrophoretic light scattering. The membrane properties were measured by fluorescence spectroscopy – especially generalized polarization (Laurdan) and anisotropy (Diphenylhexatriene). The same characteristic of liposomes was measured after the nebulization by vibrating mesh nebulizer. Cholesterol was capable of liposome stabilization because of increased membrane fluidity. The membrane properties of the outer and inner parts were not influenced by the nebulization process. Electrostatic stabilization was successful for the lowest concentration of phosphatidic acid, but after the nebulization process the hydration of the membrane outer part was changed. Higher amount of PEG needs to be added for successful steric stabilization. The nebulization process of the two lowest concentrations of PEG slightly influenced immobilized water and the rigidity of inner part of the membrane (especially around the phase transition temperature).

Evaluation of Aerosol Therapy during the Escalation of Care in a Model of Adult Cystic Fibrosis.

Lung disease is the main cause of morbidity and mortality in cystic fibrosis (CF). CF patients inhale antibiotics regularly as treatment against persistent bacterial infections. The goal of this study was to investigate the effect of clinical intervention on aerosol therapy during the escalation of care using a bench model of adult CF. Droplet size analysis of selected antibiotics was completed in tandem with the delivered aerosol dose (% of total dose) assessments in simulations of various interventions providing oxygen supplementation or ventilatory support. Results highlight the variability of aerosolised dose delivery. In the homecare setting, the vibrating mesh nebuliser (VMN) delivered significantly more than the jet nebuliser (JN) (16.15 ± 0.86% versus 6.51 ± 2.15%). In the hospital setting, using VMN only, significant variability was seen across clinical interventions. In the emergency department, VMN plus mouthpiece (no supplemental oxygen) was seen to deliver (29.02 ± 1.41%) versus low flow nasal therapy (10 L per minute (LPM) oxygen) (1.81 ± 0.47%) and high flow nasal therapy (50 LPM oxygen) (3.36 ± 0.34%). In the ward/intensive care unit, non-invasive ventilation recorded 19.02 ± 0.28%, versus 22.64 ± 1.88% of the dose delivered during invasive mechanical ventilation. These results will have application in the design of intervention-appropriate aerosol therapy strategies and will be of use to researchers developing new therapeutics for application in cystic fibrosis and beyond.

Comparison of Vibrating Mesh and Jet Nebulizers During Noninvasive Ventilation in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Background: Advances in aerosol technology have improved drug delivery efficiency during noninvasive ventilation (NIV). Clinical evaluation of the efficacy of aerosol therapy during NIV in the treatment of acute exacerbation of chronic obstructive pulmonary disease (COPD) is very limited. The aim of our study was to compare the efficacy of bronchodilators administered through a vibrating mesh nebulizer (VMN) and jet nebulizer (JN) during NIV in patients with acute exacerbation of COPD. Methods: Prospective randomized cross-over study included 30 patients treated with NIV for acute exacerbation of COPD in an acute care hospital. Patients were consented and enrolled after stabilization of acute exacerbation (3-5 days after admission). Subjects were randomly assigned into two treatment arms receiving salbutamol (2.5 mg): with VMN (Aerogen Solo) and JN (Sidestream) positioned between the leak port and the nonvented oronasal mask during bilevel ventilation with a single-limb circuit. Measurements (clinical data, pulmonary function tests [PFTs], and arterial blood gases) were performed at baseline, 1, and 2 hours after treatment. Results: All measured PFT parameters significantly increased in both groups, but numerically results were better after inhalation with VMN than with JN: for forced expiratory volume in 1 second (FEV1) (mean increase from baseline to 120 minutes-165 ± 64 mL vs. 116 ± 46 mL, p = 0.001) and for forced vital capacity (FVC) (mean increase-394 ± 154 mL vs. 123 ± 57 mL, p < 0.001). There was also a statistically significant reduction in respiratory rate and in Borg dyspnea score after therapy with VMN in comparison with the conventional JN. In both groups, there were improvements in PaCO2, but with VMN these changes were significantly higher. Conclusion: Bronchodilator administration in patients with acute exacerbation of COPD during NIV with VMN resulted in clinically significant improvements in FVC and in Borg dyspnea score. Additional studies required to determine the impact on clinical outcomes.

The Effect of Different Interfaces on the Aerosol Delivery with Vibrating Mesh Nebulizer During Noninvasive Positive Pressure Ventilation

Background: The effect of different interfaces on the aerosol delivery with vibrating mesh nebulizer during noninvasive positive pressure ventilation (NIV) is not clear. Materials and Methods: Noninvasive ventilator and four interfaces were connected to IngMar ASL 5000 lung simulator. Meanwhile, the vibrating mesh nebulizer was connected to a ventilator circuit to simulate the nebulization during noninvasive ventilation. The nebulizer position was placed at proximal position (near the mask) and distal position (15 cm away from the mask); the inspiratory positive airway pressure (IPAP) and the expiratory positive airway pressure (EPAP) were set to 16/4, 16/8, 20/4, and 20/8 cmH2O, respectively. The aerosol was collected through a disposable filter placed between the simulated lung and the mask, after which the aerosol delivery was calculated. Meanwhile, we recorded the inspiratory tidal volume and the mean inspiratory flow. Results: The aerosol delivery varied between 1.7% ± 0.0% and 21.1% ± 1.1%. Only when EPAP was set to 4 cmH2O, the statistical difference in aerosol delivery was observed between the two types of interface, and between different leak port locations (p < 0.01; p = 0.04, respectively). When IPAP/EPAP was set to 16/4 and 20/4 cmH2O, respectively, at different nebulizer positions, there was a statistical difference between the interface with the same type but different leak port locations and between the interface with same leak port location but different inner volumes (all p < 0.01). Also, there was a correlation between the aerosol delivery and interface volume (p < 0.01, R2 = 0.55; p < 0.01, R2 = 0.51, respectively), and between aerosol delivery and the intentional leak of interfaces (p < 0.01, R2 = 0.59; p < 0.01, R2 = 0.48, respectively). When EPAP was set to 4 and 8 cmH2O, respectively, the aerosol delivery of nebulizer distal position was significantly higher than that of proximal position (12.2% ± 5.0% vs. 9.1% ± 4.1%, p < 0.05; 2.5% ± 0. 5% vs. 2.1% ± 0.3%, p < 0.01, respectively). Conclusion: Interfaces have a significant effect on aerosol delivery during NIV. The interfaces with different inner volumes, intentional leak, and leak port location may all have an effect on aerosol delivery. The addition of a 15 cm tube between the nebulizer and the mask significantly increases the aerosol delivery.