Vibrating Mesh Nebulizer Research Articles

Targeted delivery of flagellin by nebulization offers optimized respiratory immunity and defense against pneumococcal pneumonia.

Novel therapeutic strategies are urgently needed to combat pneumonia caused by Streptococcus pneumoniae strains resistant to standard-of-care antibiotics. Previous studies have shown that targeted stimulation of lung innate immune defenses through intranasal administration of the Toll-like receptor 5 agonist flagellin improves the treatment of pneumonia when combined with antibiotics. To promote translation to the clinic application, this study assessed the direct delivery of flagellin to the airways through nebulization using a vibrating mesh nebulizer in mice. Intranasal delivery achieved approximately 40% lung deposition of the administered flagellin dose, whereas nebulization yielded less than 1%. Despite these differences, nebulized flagellin induced transient activation of lung innate immunity characterized by cytokine/chemokine production and neutrophil infiltration into airways analogous to intranasal administration. Furthermore, inhalation by nebulization resulted in an accelerated resolution of systemic pro-inflammatory responses. Lastly, adjunct therapy combining nebulized flagellin and amoxicillin proved effective against antibiotic-resistant pneumococcal pneumonia in mice. We posit that flagellin aerosol therapy represents a safe and promising approach to address bacterial pneumonia within the context of antimicrobial resistance.

Performance of newly developed add-on devices on aerosol delivery in noninvasive ventilated subjects

Background: Several techniques had been developed to generate aerosolized medications during noninvasive ventilation (NIV) using variable inhalation methods. This study hypothesized that large spacers were more efficient significantly than small spacers and adapters during NIV. Objective: The main objective of this study was to compare the performance of newly developed spacers with standard T-piece in NIV chronic obstructive pulmonary disease (COPD) subjects. Methods: Sixty COPD subjects requiring NIV were included in this study. A dual-limb circuit was used, and the mode of ventilator was set in spontaneous volume-controlled mode. Dual-limb ventilation circuit, consists of inspiratory-limb and expiratory-limb, is pressure and volume controlled in response to subject expiration providing relatively high resistance to expiratory flow. Two experimental sets were evaluated: the first was introducing two preliminary pressurized metered-dose inhalers (pMDI) puffs before the nebulization of 1 ml of a respirable solution of salbutamol by vibrating mesh nebulizer (VMN) using Minimhal and Combihaler. The second was to only nebulize 1 ml of salbutamol respirable solution by VMN using Combihaler, Minimhal, and standard T-piece. Two urine samples were collected after aerosol delivery: urine sample after 30 min. (USAL0.5) as an indicator of lung deposition and all urine pooled 24 h (USAL24) post-inhalation as an indicator of systemic absorption. The amount of salbutamol extracted from urine samples was assayed by high-performance liquid chromatography. Results: Minimhal + pMDI + VMN delivered a higher percentage of salbutamol 30 min post-inhalation than Minimhal + VMN (p < 0.001). Also, Combihaler + pMDI + VMN delivered a higher percentage of salbutamol 30 min post-inhalation than Combihaler + VMN (p < 0.001). Combihaler + VMN delivered a higher percentage of salbutamol 30 min and 24 h post-inhalation than both Minimhal + VMN and T-piece + VMN (p < 0.001). Standard T-piece delivered the lowest aerosol amount delivered to the lung compared to both spacers (p < 0.05). Conclusions: Introducing two pMDI puffs significantly improved aerosol delivery by both spacers. Combihaler significantly improves aerosol delivery more than Minimhal.

Respiratory Delivery of Lacticaseibacillus rhamnosus GG by Vibrating-Mesh and Jet Nebulisation

Background: The use of probiotic bacteria to improve lung health has been gaining interest. Although the oral delivery of probiotics and their effects are well documented, there is currently limited knowledge on the respiratory delivery of probiotics. Objectives: This study aimed to investigate whether nebulisation is suitable for delivering Lacticaseibacillus rhamnosus GG (LGG) into the lungs for the potential treatment of bacterial pulmonary infections. Methods: It compared the dose output and aerosol performance of a vibrating-mesh nebuliser (VMN) and a jet nebuliser (JN) in nebulising LGG suspended in de Man Rogosa Sharpe (MRS) broth, phosphate-buffered saline (PBS), or normal saline (0.9% w/v sodium chloride in water). Results: The VMN consistently produced a higher output than the JN for all liquid media, indicating that VMN was more efficient. The fine-particle fractions of both nebulisers were comparable for a given medium. The highest fine-particle fraction was achieved with LGG suspended in MRS broth for both nebulisers (20.5 ± 2.8% for VMN; 18.7 ± 3.4% for JN). This suggests that the aerosol performance of nebulised probiotics may depend on the medium in which the probiotic bacteria were suspended. Conclusions: Therefore, this study demonstrated that the nebulisation efficiency of LGG depended on the nebuliser type and liquid medium of the probiotic suspension.

Alveolar distribution of nebulized solution in health and lung injury assessed by confocal microscopy.

Parenchymal distribution of nebulized drug in healthy and diseased lungs has not, as evident from a literature review, been well characterized. We use a vibrating mesh nebulizer to deliver fluorescein solution invivo to healthy or intratracheal-lipopolysaccharide (LPS)-instilled anesthetized rats in dorsal recumbency, or exvivo to the lungs of LPS-instilled rats. Following invivo nebulization (healthy/LPS-instilled), we quantify fluorescein intensity distribution by confocal microscopy in standard locations on the surface of freshly isolated lungs. Following LPS instillation (in vivo/ex vivo nebulization), we quantify fluorescein intensity in visibly injured locations. In standard locations, there is uniform, low-intensity basal fluorescein deposition. Focal regions receive high deposition that is, in upper (cranial), middle, and lower (caudal) locations, 6.4 ± 4.9, 3.3 ± 3.0, and 2.3 ± 2.8 times greater, respectively, than average basal intensity. Following LPS instillation, deposition in moderately injured regions can be high or low; deposition in severely injured regions is low. Further, actively phagocytic cells are observed in healthy and LPS-instilled lungs. And LPS particularly impairs mechanics and activates phagocytic cells in the male sex. We conclude that a low level of nebulized drug can be distributed across the parenchyma excepting to severely injured regions.

Detectable Concentrations With Inhaled Tobramycin in Critically Ill Infants and Children Following Implementation of Standardized Protocol.

A protocol was established for ventilator-associated tracheitis or pneumonia using inhaled tobramycin 300 mg every 12 hours in mechanically ventilated children via a vibrating mesh nebulizer, 30 cm from the endotracheal tube in the inspiratory loop of the mechanical ventilator. The primary objective was to determine the incidence of detectable tobramycin trough concentrations >0.5 µg/mL. Secondary objectives included a comparison of clinical characteristics between those with and without detectable concentrations and identification of patients with acute kidney injury (AKI) as defined by the Kidney Diseases Improving Global Outcomes (KDIGO) criteria. This was a single-center retrospective study of critically ill children <18 years without cystic fibrosis receiving inhaled tobramycin between July 1, 2016, and August 31, 2021. Data collection included demographics, tobramycin regimen, and renal function. Analysis was performed using SAS 9.4, with a P-value <0.05, and a multivariable regression model was performed to identify factors for detectable concentrations and AKI. Forty-four patients (66 courses) were included, with an overall age of 0.83 years. Thirty (68%) patients had detectable concentrations and 9 (20.5%) developed AKI. No significant differences in demographics, diagnosis, mechanical ventilation settings, and number of nephrotoxins were noted between those with and without detectable concentrations or AKI. Multivariable regressions did not identify factors associated with detectable concentrations or AKI. Detectable concentrations occurred with the majority of courses, with AKI associated with approximately one-fourth of courses. Clinicians should consider utilizing trough monitoring for all mechanically ventilated critically ill children receiving inhaled tobramycin.

Microbubble-laden aerosols improve post-nasal aerosol penetration efficiency in a preterm neonate model

Nebulized lung surfactant therapy has been a neonatology long-pursued goal. Nevertheless, many clinical trials have yet to show a clear clinical efficacy of nebulized surfactant, which, in part, is due to the technical challenges of delivering aerosols to the lungs of preterm neonates. The study aimed to test microbubbles for improving lung deposition in preterm neonates. An in vitro testing method was developed to replicate the clinical environment; it used a 3D-printed preterm neonate model, connected to a high-flow nasal cannula (HFNC) and a vibrating mesh nebulizer. The flow rate of the HFNC mirrored that used in the clinics (i.e., 4, 6, and 8 L/min). Followingly, the lung penetrations of aerosols with and without microbubbles were compared. The aerodynamic diameter of aerosols with microbubbles (MMAD=1.75 μm) was lower than that of the counterpart (MMAD=2.25 μm). Microbubble-laden aerosols had a significantly higher number of microbubbles that were below 1.0 μm. Microbubble-laden aerosols had dramatically higher lung penetration in the preterm model; lung penetration efficiencies were 30.0, 25.5, and 17.5 % at 4, 6, and 8 L/min, respectively, whereas the lung penetration efficiency for conventionally nebulized aerosols was below 1.25 % in the three flow rates.

Nebulized Budesonide Prevents Airway Inflammation in Children with High Total IgE Levels After Open Heart Surgery with Cardiopulmonary Bypass: A Prospective Randomized Controlled Trial.

Cardiopulmonary bypass (CPB) is a crucial technique used to repair congenital heart defects (CHD); however, it may induce inflammatory response, leading to airway inflammation and need for prolonged mechanical ventilation. In this study, we aimed to evaluate the effect of budesonide nebulization in children with high serum total immunoglobulin E (tIgE) levels undergoing surgical repair of CHD via CPB. We conducted a randomized, single-center, controlled trial at a tertiary teaching hospital. One-hundred and one children with high tIgE were enrolled and randomized into the budesonide nebulization group (BUD group, n = 50) or the normal saline nebulization group (NS group, n = 51) between January 2020 and December 2020. Budesonide or normal saline was administered through a vibrating mesh nebulizer during mechanical ventilation every 8h. Blood and bronchoalveolar lavage fluid (BALF) samples were examined and data on airway mechanics and clinical outcomes were recorded. IL-6 and IL-8 levels in the blood and BALF samples significantly increased after CPB in both groups. Budesonide inhalation reduced IL-6 and IL-8 levels in the blood and BALF samples in children with high tIgE (P < 0.05). The mean airway pressure, PCO2, and oxygen index in the BUD group were significantly lower than those in the NS group after the first inhalation dose and persisted until almost 24h after surgery. The peak inspiratory pressure and drive pressure were lower in the BUD group than in the NS group at nearly 24h after surgery, with no significant difference at other time points. Additionally, the duration of mechanical ventilation, number of noninvasive ventilations after extubation, and number of patients using aerosol-inhaled bronchodilators after CICU in the BUD group were significantly lower than those in the NS group (P < 0.05). Children with high preoperative tIgE levels are at risk of airway inflammation after cardiopulmonary bypass. Inhaling budesonide during postoperative mechanical ventilation can reduce the intensity of inflammatory reactions, shorten the duration of mechanical ventilation, reduce airway pressure and the utilization of NIV after extubation.

Are Hydroxyl Radicals Spontaneously Generated in Unactivated Water Droplets?

Spontaneous ionization/breakup of water at the surface of aqueous droplets has been reported with evidence ranging from formation of hydrogen peroxide and hydroxyl radicals, indicated by ions at m/z 36 attributed to OH•‐H3O+ or (H2O‐OH2)+• as well as oxidation products of radical scavengers in mass spectra of water droplets formed by pneumatic nebulization. Here, aqueous droplets are formed both by nanoelectrospray, which produces highly charged nanodrops with initial diameters ~100 nm, and a vibrating mesh nebulizer, which produces 2 – 20 µm droplets that are less highly charged. The lifetimes of these droplets range from 10s of µs to 560 ms and the surface‐to‐volume ratios span ~100‐fold range. No ions at m/z 36 are detected with pure water, nor are significant oxidation products for the two radical scavengers that were previously reported to be formed in high abundance. These and other results indicate that prior conclusions about spontaneous hydroxyl radical formation in unactivated water droplets are not supported by the evidence and that water appears to be stable at droplet surfaces over a wide range of droplet size, charge and lifetime.

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.

Anticancer drug delivery: Investigating the impacts of viscosity on lipid-based formulations for pulmonary targeting

Pulmonary drug delivery via aerosolization is a non-intrusive method for achieving localized and systemic effects. The aim of this study was to establish the impact of viscosity as a novel aspect (i.e., low, medium and high) using various lipid-based formulations (including liposomes (F1-F3), transfersomes (F4-F6), micelles (F7-F9) and nanostructured lipid carriers (NLCs; F10-F12)) as well as to investigate their impact on in-vitro nebulization performance using Trans-resveratrol (TRES) as a model anticancer drug. Based on the physicochemical properties, micelles (F7-F9) elicited the smallest particle size (12–174 nm); additionally, all formulations tested exhibited high entrapment efficiency (>89 %). Through measurement using capillary viscometers, NLC formulations exhibited the highest viscosity (3.35–10.04 m2/sec). Upon using a rotational rheometer, formulations exhibited shear-thinning (non-Newtonian) behaviour. Air jet and vibrating mesh nebulizers were subsequently employed to assess nebulization performance using an in-vitro model. Higher viscosity formulations elicited a prolonged nebulization time. The vibrating mesh nebulizer exhibited significantly higher emitted dose (ED), fine particle fraction (FPF) and fine particle dose (FPD) (up to 97 %, 90 % and 64 µg). Moreover, the in-vitro release of TRES was higher at pH 5, demonstrating an alignment of the release profile with the Korsmeyer-Peppas model. Thus, formulations with higher viscosity paired with a vibrating mesh nebulizer were an ideal combination for delivering and targeting peripheral lungs.

A Pediatric Bench Model of Continuous Albuterol Delivery Using Heliox.

The optimal setup for continuously administering albuterol with heliox remains unclear, especially for pediatric patients. This study aimed to evaluate the efficiency of continuous albuterol delivery with heliox using different nebulizer setups in a pediatric model. A pediatric manikin with simulated spontaneous breathing was used to receive continuous albuterol (20 mg/h) with heliox (80/20) in 3 setups: (1) The MiniHEART nebulizer, driven by oxygen at 3 L/min, was attached to a Y-piece, linking to a non-rebreather mask and a valved reservoir with 11 L/min heliox; (2) a vibrating mesh nebulizer (VMN) placed at the humidifier inlet of high-flow nasal cannula (HFNC) with 11 L/min heliox and the manikin's mouth sealed; and (3) a VMN placed between a valved reservoir with 11 L/min heliox and a non-rebreather mask. Both tight-fitting and loose-fitting mask configurations were tested in the setup with vibrating mesh nebulizer and mask. Heliox of 70/30 was tested with a VMN and a loose-fitting mask. Albuterol was delivered continuously to the nebulizer via an infusion pump at 8 mL (20 mg)/h for each 20-min run and each experiment was repeated five times. A collecting filter placed between the manikin's trachea and lung model was removed after each run, and the drug was eluted and assayed via ultraviolet spectrophotometry (276 nm). During continuous albuterol nebulization using heliox, the VMN either in line with HFNC or with a tight-fitting mask achieved the highest and similar inhaled dose (8.5 ± 0.4 vs 8.8 ± 0.7%, P = .35), while the MiniHEART nebulizer yielded the lowest aerosol deposition (1.5 ± 0.2%). The inhaled dose was lower with the loose-fitting mask than with the tight-fitting mask (5.9 ± 0.9 vs 8.8 ± 0.7%, P=.009), and heliox of 80/20 delivered a higher inhaled dose than heliox of 70/30 (5.9 ± 0.9 vs 3.9 ± 0.4%, P=.009). When administering continuous albuterol with heliox in a pediatric model, utilizing a VMN in line with HFNC during closed-mouth breathing yielded a higher inhaled dose compared to both the MiniHEART nebulizer and VMN with a loose-fitting mask.

Numerical simulation of a nebulizer with multiple orifices

A vibrating mesh nebulizer is a medical device that can break liquid medication into an aerosol of tiny droplets so that patients can inhale them to treat diseases. The volumetric flow rate of this kind of nebulizer is determined by many factors, including the orifice geometry, the vibration amplitude and the vibration mode shape. Thus, many experiments were designed to assess the effects of these different variables on flow rate and to find the optimal set of device parameters that maximizes the flow rate. However, it can be very expensive to perform such physical experimentation with physical prototypes, which needs different orifice geometries to be fabricated for different test regimes. The orifice sizes are microscopic with diameters typically between 3 µm and 5 µm, thus, they are difficult to be fabricated with the exact shape and diameter that are required. Therefore, virtual prototyping by means of numerical simulation models are required as the orifice geometries and other factors can be easily changed in the simulation models. This study aims to provide a numerical simulation model that is experimentally validated. By comparing the simulated flow rates with the experimentally obtained flow rates, and the simulated droplet diameters with the experimentally obtained droplet diameters, it was found that the errors are all less than 10 % which demonstrates this numerical simulation model is adequately validated by experiment. Thus, instead of carrying out expensive experiments, this simulation model can be used for predicting the volumetric flow rates for different prescribed orifice geometries. Furthermore, this paper also simulates the effects of viscosity and surface tension on the flow rate, where either viscosity or surface tension increases, the flow rate will decrease.

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.

Comparative Efficacy of Inhaled and Intravenous Corticosteroids in Managing COVID-19-Related Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition in which the lungs fail to provide sufficient oxygen to the body's vital organs. It is commonly associated with COVID-19 patients. Severe cases of COVID-19 can lead to lung damage and organ failure due to an immune response in the body. To mitigate these effects, corticosteroids, which are known for their anti-inflammatory properties, have been suggested as a potential treatment option. The primary focus of this study was to assess the impact of various corticosteroid administration methods on the outcomes of patients with COVID-19. Methods: The current study was conducted on COVID-19 patients divided into three groups. The first group was administered 6 mg of intravenous (IV) dexamethasone; the second group received 1 mg/kg of IV methylprednisolone (methylprednisolone); and the third group received budesonide respirable solution at a dosage of 1mg twice daily. The neubilizer used was a vibrating mesh nebulizer (VMN). All patients received standard care. We found that dexamethasone administered intravenously led to a significant reduction in C-reactive protein levels, surpassing the effectiveness of both IV methylprednisolone and inhaled budesonide. Oxygen saturation without mask change over time showed statistically significant differences (p = 0.004) in favor of the budesonide and dexamethasone groups for all days. Individuals who received methylprednisolone showed a significant decrease in mortality rate and an extended survival duration, with statistical significance observed at p = 0.024. The rest of the parameters, including ferritin, lymphocytes, total leukocyte count, platelets, hemoglobin, urea, serum potassium, serum sodium, serum creatinine, serum glutamic-pyruvic transaminase, serum glutamic-oxaloacetic transaminase, uric acid, albumin, globulin, erythrocyte sedimentation rate, international normalized ratio, oxygen saturation with flow, and oxygen flow, showed no statistically significant differences between the three drugs. In conclusion, treatment with IV methylprednisolone (1 mg/kg) resulted in a shorter hospital stay, decreased reliance on ventilation, and improved health outcomes for COVID-19 patients compared to using dexamethasone at a daily dosage of 6 mg or budesonide respirable solution at a dosage of 1mg twice daily.

Antisense oligonucleotides and their technical suitability to nebulization

In vivo studies investigating the inhalative efficacy of biotherapeutics, such as nucleic acids, usually do not perform an aerosolization step, rather the solution is directly administered into the lungs e.g. intratracheally. In addition, there is currently very little information on the behavior of nucleic acid solutions when subjected to the physical stress of the nebulization process.In this study, the aim was to assess the technical suitability of Locked Nucleic Acids (LNAs), as a model antisense oligonucleotide, towards nebulization using two commercially available nebulizers. A jet nebulizer (Pari LC Plus) and a vibrating mesh nebulizer (Aerogen Solo) were employed and solutions of five different LNAs investigated in terms of their physical and chemical stability to nebulization and the quality of the generated aerosols. The aerosol properties of the Aerogen Solo were mainly influenced by the viscosity of the solutions with the output rate and the droplet size decreasing with increasing viscosity. The Pari LC Plus was less susceptible to viscosity and overall the droplet size was smaller. The LNAs tolerated both nebulization processes and the integrity of the molecules was shown. Chemical stability of the molecules from the Aerogen Solo was confirmed, whereas aerosol generation with the Pari LC Plus jet nebulizer led to a slight increase of phosphodiester groups in a fully phosphorothiolated backbone of the LNAs. Overall, it could be shown that nebulization of different LNAs is possible and inhalation can therefore be considered a potential route of administration.

Impact of Nebulization on the Physicochemical Properties of Polymer-Lipid Hybrid Nanoparticles for Pulmonary Drug Delivery.

Nanoparticles (NPs) have shown significant potential for pulmonary administration of therapeutics for the treatment of chronic lung diseases in a localized and sustained manner. Nebulization is a suitable method of NP delivery, particularly in patients whose ability to breathe is impaired due to lung diseases. However, there are limited studies evaluating the physicochemical properties of NPs after they are passed through a nebulizer. High shear stress generated during nebulization could potentially affect the surface properties of NPs, resulting in the loss of encapsulated drugs and alteration in the release kinetics. Herein, we thoroughly examined the physicochemical properties as well as the therapeutic effectiveness of Infasurf lung surfactant (IFS)-coated PLGA NPs previously developed by us after passing through a commercial Aeroneb® vibrating-mesh nebulizer. Nebulization did not alter the size, surface charge, IFS coating and bi-phasic release pattern exhibited by the NPs. However, there was a temporary reduction in the initial release of encapsulated therapeutics in the nebulized compared to non-nebulized NPs. This underscores the importance of evaluating the drug release kinetics of NPs using the inhalation method of choice to ensure suitability for the intended medical application. The cellular uptake studies demonstrated that both nebulized and non-nebulized NPs were less readily taken up by alveolar macrophages compared to lung cancer cells, confirming the IFS coating retention. Overall, nebulization did not significantly compromise the physicochemical properties as well as therapeutic efficacy of the prepared nanotherapeutics.

Nebulizers.

Nebulizers generate aerosols from liquid-based solutions and suspensions. Nebulizers are particularly well suited to delivering larger doses of medication than is practical with inhalers and are used with a broad range of liquid formulations. When the same drug is available in liquid or inhaler form, nebulizers are applicable for use with patients who will not or cannot reliably use a pressurized metered-dosed inhaler (pMDI) or dry powder inhaler (DPI) due to poor lung function, hand-breath coordination, cognitive abilities (e.g., infants, elderly) or device preference. In a nebulizer, liquid medication is placed in a reservoir and fed to an aerosol generator to produce the droplets. A series of tubes and channels direct the aerosol to the patient via an interface such as mouthpiece, mask, tent, nasal prongs or artificial airway. All nebulizers contain these basic parts, although the technology and design used can vary widely and can result in significant difference in ergonomics, directions for use, and performance. While many types of nebulizers have been described, the three categories of modern clinical nebulizers include: (1) pneumatic jet nebulizers (JN); (2) ultrasonic nebulizers (USN); and (3) vibrating mesh nebulizers (VMN). Nebulizers are also described in terms of their reservoir size. Small volume nebulizers (SVNs), most commonly used for medical aerosol therapy, can hold 5 to 20 mL of medication and may be jet, ultrasonic, or mesh nebulizers. Large volume nebulizers, typically jet or ultrasonic nebulizers, hold up to 200 mL and may be used for either bland aerosol therapy or continuous drug administration.

Performance Characterisation of the Airvo2TM Nebuliser Adapter in Combination with the Aerogen SoloTM Vibrating Mesh Nebuliser for in Line Aerosol Therapy during High Flow Nasal Oxygen Therapy.

High flow oxygen (HFO) therapy is a well-established treatment in respiratory disease. Concurrent aerosol delivery can greatly expediate their recovery. The aim of this work was to complete a comprehensive characterisation of one such HFO therapy system, the Airvo2TM, used in combination with the Aerogen SoloTM vibrating mesh nebuliser. Representative adult, infant, and paediatric head models were connected to a breathing simulator via a collection filter placed at the level of the trachea. A tracheostomy interface and nasal cannulas were used to deliver the aerosol. Cannula size and gas flow rate were varied across the full operating range recommended by the manufacturer. The tracheal and emitted doses were quantified via UV-spectrophotometry. The aerosol droplet diameter at the exit of the nares and tracheal interface was measured via cascade impaction. High gas flow rates resulted in low emitted and tracheal doses (%). Nasal cannula size had no significant effect on the tracheal dose (%) available in infant and paediatric models. Higher gas flow rates resulted in smaller aerosol droplets at the exit of the nares and tracheostomy interface. Gas flow rate was found to be the primary parameter affecting aerosol delivery. Thus, gas flow rates should be kept low and where possible, delivered using larger nasal cannulas to maximise aerosol delivery.

Microfluidic Platform Enables Shearless Aerosolization of Lipid Nanoparticles for mRNA Inhalation.

Leveraging the extensive surface area of the lungs for gene therapy, the inhalation route offers distinct advantages for delivery. Clinical nebulizers that employ vibrating mesh technology are the standard choice for converting liquid medicines into aerosols. However, they have limitations when it comes to delivering mRNA through inhalation, including severe damage to nanoparticles due to shearing forces. Here, we introduce a microfluidic aerosolization platform (MAP) that preserves the structural and physicochemical integrity of lipid nanoparticles, enabling safe and efficient delivery of mRNA to the respiratory system. Our results demonstrated the superiority of the MAP over the conventional vibrating mesh nebulizer, as it avoided problems such as particle aggregation, loss of mRNA encapsulation, and deformation of the nanoparticle morphology. Notably, aerosolized nanoparticles generated by the microfluidic device led to enhanced transfection efficiency across various cell lines. In vivo experiments with mice that inhaled these aerosolized nanoparticles revealed successful lung-specific mRNA transfection without observable signs of toxicity. This MAP may represent an advancement for the pulmonary gene therapy, enabling precise and effective delivery of aerosolized nanoparticles.

Effect of Interrupting Heated Humidification on Nebulized Drug Delivery Efficiency, Temperature, and Absolute Humidity During Mechanical Ventilation: A Multi-Lab In Vitro Study.

Introduction: During mechanical ventilation (MV), inspired gases require heat and humidification. However, such conditions may be associated with reduced aerosol delivery efficiency. The practice of turning off heated humidification before nebulization and the impact of nebulization on humidity in a dry ventilator circuit remain topics of debate. This study aimed to assess the effect of turning off heated humidification on inhaled dose and humidity with nebulizer use during adult MV. Methods: A bronchodilator (albuterol) and two antibiotics (Colistimethate sodium and Amikacin sulfate) were nebulized with a vibrating mesh nebulizer placed at the humidifier inlet and in the inspiratory limb at the Y-piece. Additionally, albuterol was nebulized using a jet nebulizer in both placements. Aerosol particle size distribution was determined through a cascade impactor. Absolute humidity (AH) and temperature of inspired gases were determined with anemometer/hygrometers before, during, and after nebulization, before, during, and up to 60 minutes after interrupting active humidification. Aerosol collected on a filter distal to the endotracheal tube and on impactor stages were eluted and assayed by spectrophotometry. Results: The inhaled dose was greater when both nebulizers were placed at the humidifier inlet than the inspiratory limb at the Y-piece. Irrespective of the nebulizer types and placements, the inhaled dose either decreased or showed no significant change after the humidifier was turned off. The aerosol particle size ranged from 1.1 to 2.7 μm. With interruption of active humidification, humidity of inspired gas quickly dropped below recommended levels, and nebulization in dry ventilator circuit produced an AH between 10 and 20 mgH2O/L, lower than the recommended minimum of 30 mgH2O/L. Conclusion: Interrupting active humidification during MV before nebulization did not improve aerosol delivery efficiency for bronchodilator or antibiotics, but did reduce humidity below recommended levels.