Mass Median Aerodynamic Diameter Research Articles

Influence of puff topographies on e-liquid heating temperature, emission characteristics and modeled lung deposition of Puff Bar™.

Puff Bar™, one of the latest designs of e-cigarettes, heats a mixture of liquid using a battery-powered coil at certain temperatures to emit aerosol. This study presents a mass-based characterization of emissions from seven flavors of Puff Bar™ devices by aerosolizing with three puff topographies [(puff volume: 55 < 65 < 75-mL) within 4-seconds at 30-seconds interval]. We evaluated the effects of puff topographies on heating temperatures; characterized particles using a cascade impactor; and measured volatile carbonyl compounds (VCCs). Modeled dosimetry and calculated mass median aerodynamic diameters (MMADs) were used to estimate regional, total respiratory deposition of the inhaled aerosol and exhaled fractions that could pose secondhand exposure risk. Temperatures of Puff Bar™ e-liquids increased with increasing puff volumes: 55mL (116.6 °C), 65 mL (128.3 °C), and 75mL (168.9 °C). Flavor types significantly influenced MMADs, total mass of particles, and VCCs (μg/puff: 2.15-2.30) in Puff Bar™ emissions (p < 0.05). Increasing puff volume (mL:55 < 65 < 75) significantly increased total mass (mg/puff: 4.6 < 5.6 < 6.2) of particles without substantially changing MMADs (~1μm:1.02~0.99~0.98). Aerosol emissions were estimated to deposit in the pulmonary region of e-cigarette user (41-44%), which could have toxicological importance. More than 2/3 (67-77%) of inhaled particles were estimated to be exhaled by users, which could affect bystanders. The VCCs measured contained carcinogens-formaldehyde (29.6%) and acetaldehyde (16.4%)-as well as respiratory irritants: acetone (23.9%), isovaleraldehyde (14.5%), and acrolein (4.9%). As Puff Bar™ emissions contain respirable particles and harmful chemicals, efforts should be made to minimize exposures, especially in indoor settings where people (including vulnerable populations) spend most of their life-time.

Engineering of inhalable nano-in-microparticles for co-delivery of small molecules and miRNAs

In this study, novel Trojan particles were engineered for direct delivery of doxorubicin (DOX) and miR-34a as model drugs to the lungs to raise local drug concentration, decrease pulmonary clearance, increase lung drug deposition, reduce systemic side effects, and overcome multi-drug resistance. For this purpose, targeted polyelectrolyte nanoparticles (tPENs) developed with layer-by-layer polymers (i.e., chitosan, dextran sulfate, and mannose-g-polyethyleneimine) were spray dried into a multiple-excipient (i.e., chitosan, leucine, and mannitol). The resulting nanoparticles were first characterized in terms of size, morphology, in vitro DOX release, cellular internalization, and in vitro cytotoxicity. tPENs showed comparable cellular uptake levels to PENs in A549 cells and no significant cytotoxicity on their metabolic activity. Co-loaded DOX/miR-34a showed a greater cytotoxicity effect than DOX-loaded tPENs and free drugs, which was confirmed by Actin staining. Thereafter, nano-in-microparticles were studied through size, morphology, aerosolization efficiency, residual moisture content, and in vitro DOX release. It was demonstrated that tPENs were successfully incorporated into microspheres with adequate emitted dose and fine particle fraction but low mass median aerodynamic diameter for deposition into the deep lung. The dry powder formulations also demonstrated a sustained DOX release at both pH values of 6.8 and 7.4.

Development and Optimisation of Inhalable EGCG Nano-Liposomes as a Potential Treatment for Pulmonary Arterial Hypertension by Implementation of the Design of Experiments Approach.

Epigallocatechin gallate (EGCG), the main ingredient in green tea, holds promise as a potential treatment for pulmonary arterial hypertension (PAH). However, EGCG has many drawbacks, including stability issues, low bioavailability, and a short half-life. Therefore, the purpose of this research was to develop and optimize an inhalable EGCG nano-liposome formulation aiming to overcome EGCG's drawbacks by applying a design of experiments strategy. The aerodynamic behaviour of the optimum formulation was determined using the next-generation impactor (NGI), and its effects on the TGF-β pathway were determined using a cell-based reporter assay. The newly formulated inhalable EGCG liposome had an average liposome size of 105 nm, a polydispersity index (PDI) of 0.18, a zeta potential of -25.5 mV, an encapsulation efficiency of 90.5%, and a PDI after one month of 0.19. These results are in complete agreement with the predicted values of the model. Its aerodynamic properties were as follows: the mass median aerodynamic diameter (MMAD) was 4.41 µm, the fine particle fraction (FPF) was 53.46%, and the percentage of particles equal to or less than 3 µm was 34.3%. This demonstrates that the novel EGCG liposome has all the properties required to be inhalable, and it is expected to be deposited deeply in the lung. The TGFβ pathway is activated in PAH lungs, and the optimum EGCG nano-liposome inhibits TGFβ signalling in cell-based studies and thus holds promise as a potential treatment for PAH.

Aluminum-based metal–organic framework nanoparticles as pulmonary vaccine adjuvants

The adoption of pulmonary vaccines to advantageously provide superior local mucosal protection against aerosolized pathogens has been faced with numerous logistical and practical challenges. One of these persistent challenges is the lack of effective vaccine adjuvants that could be well tolerated through the inhaled route of administration. Despite its widespread use as a vaccine adjuvant, aluminum salts (alum) are not well tolerated in the lung. To address this issue, we evaluated the use of porous aluminum (Al)-based metal–organic framework (MOF) nanoparticles (NPs) as inhalable adjuvants. We evaluate a suite of Al-based MOF NPs alongside alum including DUT-4, DUT-5, MIL-53 (Al), and MIL-101-NH2 (Al). As synthesized, MOF NPs ranged between ~ 200 nm and 1 µm in diameter, with the larger diameter MOFs matching those of commercial alum. In vitro examination of co-stimulatory markers revealed that the Al-based MOF NPs activated antigen presenting cells more effectively than alum. Similar results were found during in vivo immunizations utilizing ovalbumin (OVA) as a model antigen, resulting in robust mucosal humoral responses for all Al MOFs tested. In particular, DUT-5 was able to elicit mucosal OVA-specific IgA antibodies that were significantly higher than the other MOFs or alum dosed at the same NP mass. DUT-5 also was uniquely able to generate detectable IgG2a titers, indicative of a cellular immune response and also had superior performance relative to alum at equivalent Al dosed in a reduced dosage vaccination study. All MOF NPs tested were generally well-tolerated in the lung, with only acute levels of cellular infiltrates detected and no Al accumulation; Al content was largely cleared from the lung and other organs at 28 days despite the two-dose regime. Furthermore, all MOF NPs exhibited mass median aerodynamic diameters (MMADs) of ~ 1.5–2.5 µm when dispersed from a generic dry powder inhaler, ideal for efficient lung deposition. While further work is needed, these results demonstrate the great potential for use of Al-based MOFs for pulmonary vaccination as novel inhalable adjuvants.Graphical

Aerosolizable Plasmid DNA Dry Powders Engineered by Thin-film Freezing.

This study was designed to test the feasibility of using thin-film freezing (TFF) to prepare aerosolizable dry powders of plasmid DNA (pDNA) for pulmonary delivery. Dry powders of pDNA formulated with mannitol/leucine (70/30, w/w) with various drug loadings, solid contents, and solvents were prepared using TFF, their aerosol properties (i.e., mass median aerodynamic diameter (MMAD) and fine particle fraction (FPF)) were determined, and selected powders were used for further characterization. Of the nine dry powders prepared, their MMAD values were about 1-2µm, with FPF values (delivered) of 40-80%. The aerosol properties of the powders were inversely correlated with the pDNA loading and the solid content in the pDNA solution before TFF. Powders prepared with Tris-EDTA buffer or cosolvents (i.e., 1,4-dioxane or tert-butanol in water), instead of water, showed slightly reduced aerosol properties. Ultimately, powders prepared with pDNA loading at 5% (w/w), 0.25% of solid content, with or without Tris-EDTA were selected for further characterization due to their overall good aerosol performance. The pDNA powders exhibited a porous matrix structure, with a moisture content of < 2% (w/w). Agarose gel electrophoresis confirmed the chemical integrity of the pDNA after it was subjected to TFF and after the TFF powder was actuated. A cell transfection study confirmed that the activity of the pDNA did not change after it was subjected to TFF. It is feasible to use TFF to produce aerosolizable pDNA dry powder for pulmonary delivery, while preserving the integrity and activity of the pDNA.

Solubility Enhancement and Inhalation Delivery of Cyclodextrin-Based Inclusion Complex of Delamanid for Pulmonary Tuberculosis Treatment.

Tuberculosis (TB) is a contiguous airborne disease caused by Mycobacterium tuberculosis (M.tb), primarily affecting the human lungs. The progression of drug-susceptible TB to drug-resistant strains, MDR-TB and XDR-TB, has become a global challenge toward eradicating TB. Conventional TB treatment involves frequent dosing and prolonged treatment regimens predominantly by an oral or invasive route, leading to treatment-related systemic adverse effects and patient's noncompliance. Pulmonary delivery is an attractive option as we could reduce dose, limit systemic side-effects, and achieve rapid onset of action. Delamanid (DLD), an antituberculosis drug, has poor aqueous solubility, and in this study, we aim to improve its solubility using cyclodextrin complexation. We screened different cyclodextrins and found that HP-β-CD resulted in a 54-fold increase in solubility compared to a 27-fold and 13-fold increase by SBE-β-CD and HP-ɣ-CD, respectively. The stability constant (265 ± 15M-1) and complexation efficiency (8.5 × 10-4) suggest the formation of a stable inclusion complex of DLD and HP-β-CD in a 2:1 ratio. Solid-state characterization studies (DSC, PXRD, and NMR) further confirmed successful complexation of DLD in HP-β-CD. The nebulized DLD-CD complex solution showed a mass median aerodynamic diameter of 4.42 ± 0.62μm and fine particle fraction of 82.28 ± 2.79%, suggesting deposition in the respiratory airways. In bacterial studies, minimum inhibitory concentration of DLD-CD complex was significantly reduced (four-fold) compared to free DLD in M.tb (H37Ra strain). Furthermore, accelerated stability studies confirmed that the inclusion complex was stable for 4weeks with 90%w/w drug content. In conclusion, we increased the aqueous solubility of DLD through cyclodextrin complexation and improved its efficacy in vitro.

Preparation of inhalable quercetin-β-cyclodextrin inclusion complexes using the supercritical antisolvent process for the prevention of smoke inhalation-induced acute lung injury

Quercetin (Que) is a natural flavonoid with good anti-inflammatory and anti-apoptosis activities, but its poor water solubility and low bioavailability restrict its clinical application. Cyclodextrin inclusion is one effective method to improve the solubility of Que. In this study, Que-β-cyclodextrin inclusion complexes (Que-β-CD) were prepared using the supercritical antisolvent (SAS) process with supercritical carbon dioxide (SCCO2) and the grinding method, called S-Que-β-CD and G-Que-β-CD, respectively. Que-β-CD was identified with Fourier transform infrared spectroscopy and the X-ray diffraction method. S-Que-β-CD powders had a higher loading efficiency (19.81%) and drug release (71.76%), the smaller mass median aerodynamic diameter (2.83 µm), and the larger fine particle fraction (48.74%) than G-Que-β-CD powders, indicating the SAS process suitable for the preparation of Que-β-CD and S-Que-β-CD suitable for pulmonary inhalation. Pulmonary delivery of S-Que-β-CD showed good protection of the mouse lung from smoke inhalation-induced acute lung injury (SI-ALI), which was indicated by reduced pulmonary edema, high percutaneous oxygen saturation, weak inflammation and apoptosis, and the recovery of body weight. The SAS process is the optimal preparation method to obtain inhalable S-Que-β-CD powders with accelerated drug release, high lung deposition and enhanced therapeutic efficiency.

Aerosol generation by liquid jet impingement onto a solid surface

Liquid jet impinging onto a surface occurs in many industrial process such as nuclear facilities where a part of radioactive material is handled in liquid form. In the case of accidental leak of this liquid, the airborne particle release, in droplets form, is important to quantify since it is the vector of radioactive air contamination. In the literature, while droplets splashing by drop impact have been extensively studied, only few data are available concerning the airborne particle release fraction and the case of liquid jet impact is even less studied. The purpose of this work is to measure aerosol airborne release when a circular liquid jet impacts a solid surface. We found, when the liquid jet is in the Rayleigh regime, so that the jet is broken into multiple drops before impact, the inertia of the impacting drops influences the amplitude of the aerosols mass size distribution but does not change its shape and consequently the aerodynamic mass median diameter. We also show that particle airborne release depends on the impacting Weber and Ohnesorge numbers through the so-called splashing number K which characterizes the splashing transition. We finally propose a quantitative prediction of the aerosol airborne release fraction, valid for Re ∼ O(103−104) and We ∼ O(102−103), opening the way to a more general model.

Comparison of Aerosol Deposition Between a Cynomolgus Macaque and a 3D Printed Cast Model of the Animal.

Preclinical aerosol studies using animals are essential for evaluating toxic or therapeutic effects on human respiratory tract. Macaques are relevant animal models for respiratory studies, but they are sensitive, expensive and difficult-to-access. In the context of preliminary studies before animal experiments, we set up an alternative in vitro anatomical model of macaque airways to reduce, refine and replace (3Rs) the animals. We printed an in vitro anatomical cast until the third bronchial division from X-ray computed tomography data of a healthy cynomolgus macaque. This in vitro model was then connected to a respiratory pump to mimic macaque's breathing. We assessed the relevance of this in vitro model, by comparing aerosol deposition patterns obtained with the anatomical model and in three macaques using planar gamma camera imaging. DTPA-99mTechnetium aerosols were produced using three jet nebulizers, generating three different particle sizes: 13.1, 3.2 and 0.93µm in terms of the mass median aerodynamic diameter (MMAD). The data showed no statistical differences between the animal and anatomical in vitro models in terms of total aerosol deposited in the airways. However, the distribution of the deposition in the airways showed a higher deposited fraction in the upper respiratory tract in the animals than the in vitro model for all particle sizes. The anatomical printed model appears to be a relevant in vitro tool to predict total aerosol deposition in macaque airways.

Nanoparticle-containing lyophilized dry powder inhaler formulations optimized using central composite design with improved aerodynamic parameters and redispersibility

Objectives: The aim of this study was to improve the aerodynamic behavior and redispersibility of a lyophilized dry powder inhaler (DPI) formulation containing nanoparticles. Methods: Paclitaxel (PTX)-human serum albumin (HSA) nanoparticles were used as a model, and DPIs containing the nanoparticles were produced by lyophilization using different carriers and carrier ratios. A central composite design was employed to optimize the formulation. L-leucine and mannitol were chosen as independent variables, and mass median aerodynamic diameter (MMAD), emitted fraction, fine particle fraction (FPF), nanoparticle size, polydispersity index (PDI), zeta potential were selected as dependent variables. Results: The water content of DPIs was less than 5% for all DPIs. The cytotoxicity of the DPIs, determined using A549 cells, was due to PTX alone. Particle sizes of 204.3 ± 1.65 nm and 94.3–1353.0 nm were obtained before and after lyophilization, respectively. The developed method resulted in a reduction in the MMAD from 8.148 µm to 5.274 µm, an increase in the FPF from 17.63% to 33.60%, and an increase in the emitted fraction from 77.68% to 97.03%. The physico-chemical characteristics of the optimized formulation were also assessed. Conclusions: In conclusion, this study demonstrates that lyophilization can be used to produce nanoparticle-containing DPI formulations with improved redispersibility and aerodynamic properties.

Allyl isothiocyanate dry powder inhaler based on cyclodextrin-metal organic frameworks for pulmonary delivery

In this study, allyl isothiocyanate (AITC) was prepared as the dry powder inhalation by loading cyclodextrin metal-organic framework (CD-MOF) to enhance pulmonary delivery. β-CD-MOF and γ-CD-MOF both could be used to carry AITC with the optimal loading conditions (50˚C, n CD: n AITC= 1:7, 7h). Compared with β-CD-MOF, γ-CD-MOF had more advantages in AITC loading due to its high drug loading and stable crystal morphology. The particle size and the mass median aerodynamic diameter of γ-CD-MOF-AITC were accorded with the aerodynamic characteristics of lung inhalation. γ-CD-MOF-AITC might be deposited effectively in the deep lung, and the release rate of AITC reached over 90% within 5min. Meanwhile, it had good pulmonary local tolerance, permeability, and no significant toxicity. Such results indicated that γ-CD-MOF could be used as a dry powder inhaler carrier to deliver safely AITC to lung and increase its pulmonary absorption.

A hydrogel microparticle with sustained release properties for pulmonary drug delivery

Inhalable hydrogel microparticles are desirable pulmonary drug delivery systems with sustained release properties. In the present study, a hydrogel microparticle composed of Zn2+, carboxymethyl chitosan and hyaluronan aldehyde for pulmonary drug delivery has been constructed by spray drying approach. The optimized microparticles had a mean geometric particle size between 2 and 5 μm. The aerodynamics characteristic determination found the fine particle fraction approximately 40% and average mass median aerodynamic diameter of 5.5 μm. The microparticles loaded with theophylline showed a sustained drug release profile over 24 h in vitro. The formulation avoided the alveolar macrophage clearance, and had substantially longer residence time in vivo. In addition, it showed significant inflammation alleviation in the lung tissues compared with the theophyllinum only group on OVA induced asthmatic mice. In conclusion, the microparticle can be considered as a potential alternative of pulmonary drug delivery system for lung disease therapy.

The effects of 4-week inhalation exposure to titanium nitride on lungs of Sprague-Dawley rats.

Titanium nitride (TiN) is a ceramic material with physical properties such as extreme hardness, high decomposition temperature, defect structure, and gold-yellow color. TiN is generally considered non-toxic and safe; however, hazards have not been identified, especially in workers after inhalation exposure. Here, we conducted a four-week inhalation toxicity study of TiN using a nose-only inhalation exposure system in Sprague-Dawley rats. Rats were exposed to TiN for 4 weeks (6h a day, 5 days per week) at target concentrations of 45, 90, and 180mg/m3. Clinical signs, mean body weight changes, hematology, blood biochemistry, necropsy, organ weight, bronchoalveolar lavage fluid analysis, and histopathological findings were observed. Analytical concentrations of the low, middle, and high-concentration groups were 45.55 ± 3.18mg/m3, 90.69 ± 7.30mg/m3, and 183.87 ± 15.21mg/m3, respectively. The mass median aerodynamic diameter (MMAD) for the low, middle, and high-concentration groups were 1.44 ± 0.07μm, 1.47 ± 0.18μm, and 1.68 ± 0.16μm, and the geometric standard deviation (GSD) was 2.24 ± 0.03, 2.31 ± 0.16, and 2.43 ± 0.11, respectively. No systemic adverse effects were observed after inhalation exposure to TiN; however, histopathological findings (increased phagocytic macrophages and alveolar/bronchiolar epithelial hyperplasia) and Bronchoalveolar Lavage Fluid (BALF) analysis (elevated lactate dehydrogenase and gamma-glutamyltransferase values) showed adverse effects on the lungs in the middle and high-concentration groups. Based on these results, the no observed adverse effect concentration (NOAEC) is suggested to be 45mg/m3.

Beclomethasone dipropionate: efficacy and safety of the administration by nebulization.

The advent of inhaled corticosteroids (ICS) brought a revolution in the management of asthma, representing now the cornerstone in this pathological condition treatment. Indeed, these drugs have clearly shown to possess a high degree of both efficacy and safety. Beclomethasone dipropionate (BDP) is the first molecule tested in the early 1970s. When administered via nebulizers or pressurized metered-dose inhalers (pMDI), BDP was found to be effective in reducing the symptoms frequency and severity in asthmatic patients, even in those previously treated with low-dose oral corticosteroids. The drug was thus produced to be administered by nebulization or via pMDI. Nebulizers are a practical and efficient tool for administering inhaled drugs in patients of all degree of severity and belonging to all ages, but are especially useful for those unable to utilize other inhaler devices correctly. BDP aerosolization, when generated by modern pneumatic nebulizers, can deliver particles with a mass median aerodynamic diameter (MMAD) value of 2.9-3.7 µm. This ability allows the deposition of the drug in small caliber airways, and considerably reduces the amount of drug deposited in the oropharynx, thus improving this molecule pharmacokinetics. This review aims to analyze the factors influencing the efficacy and safety of ICS, evaluating in detail the characteristics of BDP administered by nebulization.

Alkaline tea tree oil nanoemulsion nebulizers for the treatment of pneumonia induced by drug-resistant Acinetobacter baumannii

The infectious pneumonia induced by drug-resistant Acinetobacter baumannii (DRAB), a hospital-acquired bacterial infection, has a high morbidity and mortality rate. A natural essential oil, tea tree oil (TTO), has a high bactericidal effect without the potential of drug resistance; however, its volatility, hydrophobicity and poor stability limit its applications. Here, TTO nanoemulsions (nanoTTOs) were prepared with the spontaneous-emulsification method. The size of nanoTTOs was 293.2 nm, and the zeta potential was −15.0 mV. They became nebulizers when they were transformed to fine aerosols with a vibrating screen nebulizer. The aerosols had a mass median aerodynamic diameter size of 2.53 μm and a fine particle fraction (1–5 μm) of 86.65%, suitable for pulmonary delivery. The minimum bactericidal concentration (MBC) of nanoTTOs against DRAB was 10.40 mg/mL; while the alkaline nanoTTOs doped with 1.0% NaHCO3 had the MBC of 6.50 mg/mL. Pulmonary delivery of the alkaline nanoTTOs showed obvious therapeutic effects on the DRAB pneumonic mice by downregulating the pro-inflammatory cytokines (IL-1β and IL-6), preventing the bacterial proliferation, and reducing the lung injury, better than ordinary nanoTTOs. Alkaline nanoTTOs are a promising nebulizer formulation for the treatment of bacterial pneumonia, especially drug-resistant bacterial pneumonia.

Performance and Feasibility of Therapeutic Vibrating Mesh Nebulizer for Ventilation Lung Scan

PurposeThis study aimed to evaluate the performance of a therapeutic vibrating mesh-type nebulizer for the pulmonary delivery of radioaerosols for lung scintigraphy in healthy subjects.MethodsSix healthy subjects (mean age of 28.7 ± 6.2 years) inhaled 2 mL Tc-99m diethylenetriaminepentaacetic acid and normal saline solution (20 mCi) via a therapeutic vibrating mesh-type nebulizer (DK010, DELBio, Taipei, Taiwan). The nebulizer’s mass median aerodynamic diameter was between 2.3 and 5.0 µm (3.47 ± 0.37 µm), and the nebulization rate was greater than 0.2 mL/min. Scintigraphy was performed to count radioaerosols in the regions of interest to determine the total and regional lung deposition and extrathoracic airway deposition of aerosols, penetration of aerosols, and radioactivity count balance (RCB).ResultsThe total lung depositions of aerosols were 21.2% ± 5.2% (% ex-valve dose), 27.4% ± 8.0% (% ex-device dose), and 13.8% ± 4.1% (% initial dose) in the nebulizer. The extrathoracic airway deposition was 4.8% ± 1.1%. The RCB was 5.4% ± 3.0%. The ratio of outer over inner lung deposition (O/I ratio, or penetration index) was 1.89 ± 0.55.ConclusionThe delivery efficiency and penetration of aerosols to the peripheral lung, which were achieved by the DELBio DK010 vibrating mesh-type nebulizer, were similar to the commercialized jet-type nebulizers dedicated for radioaerosol lung scintigraphy nebulizer. The therapeutic vibrating mesh-type nebulizer (DELBio DK010) is feasible for radionuclide lung ventilation scintigraphy.

Mechanistic Modelling of Targeted Pulmonary Delivery of Dactinomycin Iron Oxide Loaded Nanoparticles for Lung Cancer Therapy

With the increase in respiratory conditions including lung cancer post covid-19 pandemic, drug-loaded nanoparticulate dry powder inhalers (DPIs) can facilitate targeted lung delivery as a patient-friendly, non-invasive method. The aim of this work was to synthesise and optimise iron oxide nanoparticles (IONPs) containing dactinomycin as a model drug, using Quality by Design (QbD) principles. Chitosan and sodium alginate were investigated as polymeric coatings. The mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), burst-effect (BE), entrapment-efficiency (EE) and the emitted-dose (ED) were investigated in initial screening studies and outcomes used to set up a Design of Experiments (DoE). Results revealed that chitosan IONPs were superior to that of sodium alginate in delivering DPI with optimal properties [ED (89.9%), FPF (59.7%), MMAD (1.59 µm) and BE (12.7%)]. Design space for targeted IONPs included formulations containing 2.1-2.5% dactinomycin and 0.5–0.9% chitosan. Differential scanning calorimetry and X-ray diffraction and SEM-EDS analysis revealed effective formation of IONPs, and TEM images revealed the production of spherical IONPs with particle size of 4.4 ± 0.77 nm. This work overcame the light sensitivity of dactinomycin to potentially target the high molecular weight drugs to the lungs, with controlled delivery based on a reduced burst effect.

Technical features of vaping drug delivery system for bronchodilator delivery

PurposeSeveral technical features influencing bronchodilator delivery were evaluated using different vaping drug delivery systems (VDDS). MethodsTerbutaline in powder form, combined with 1, 3- propanediol used as e-liquid was tested at different concentrations (1 and 2.5 mg/mL), power levels (15 W and 30 W), and set applied resistances (0.15 to 1.5 O) to compare the efficiency of three VDDS (GS AIR2, GS TANK, CUBIS). Samples were collected with a Glass Twin Impinger (GTI). A High Performance Liquid Chromatography (HPLC) was used for drug quantification. The Next Generation Impactor (NGI) measured particle size distribution. Results were also considered with a clinical jet nebulizer (Cirrus TM 2, 2 mL of terbutaline at 2.5 mg/mL). ResultsGS AIR2 with resistance = 1.5 O; power = 15 W, and [Terbutaline] = 2.5 mg/mL represents the optimal VDDS conditions to deliver a respirable dose of 20.05 ± 4.2 µg/puff with a mass median aerodynamic diameter (MMAD) of 1.41 ± 0.03 µm. Thus, 52 puffs were required (lasting approximately 15 min of vaping) to reach similar respirable dose and MMAD compared to nebulization. ConclusionWe proved that several crucial VDDS technical parameters govern the performance of respiratory bronchodilator delivery including the resistance, power level and atomizer design.

“Novel mucoadhesive PLGA-PVM/MA micro-nanocomposites loaded with felodipine intended for pulmonary administration by nebulization”

Poly(latic-co-glycolic) acid (PLGA) nanoparticles loaded with felodipine (FEL) were embedded in a mucoadhesive matrix of poly (methyl vinyl ether-co-maleic anhydride) (PVM/MA) to prepare micro-nanoparticulate composites by particle engineering. Composites were characterized for physical and rheological properties and formulated with inhalable grade lactose. In-vitro characterization studies such as drug release kinetics, and mucoadhesive, and aerodynamic properties were performed. The in-vivo efficacy was evaluated by administering the optimized composites by nebulization in hypertensive rats. The obtained FEL-PLGA-PVM/MA composites of 1,069 ± 82 nm showed sustained drug release and mucoadhesive properties. Bulk and tapped densities of composites mixed with lactose were 0.08–0.13 g/mL and 0.18–0.30 g/mL, respectively, with mass median aerodynamic diameters (MMAD) in a range of 1.29–12.0 µm. After pulmonary administration of the composites, a decrease in systolic and diastolic blood pressure was observed within the first 3 h, of −9.0 ± 1.3 % and −13.9 ± 3.3 %, respectively, with a maximal effect at 12 h (sustained during 144 h), in contrast to pure FEL, which showed no significant decrease in blood pressure (1.6 ± 2.7 % and 4.1 ± 4.1 %). Findings suggest that novel mucoadhesive FEL-PLGA-PVM/MA composites are a promising strategy formulation to treat systemic diseases by pulmonary route.

Study on mass concentration and morphology of SMAW fume particles with a new covered electrode using nano-CaTiO3 as an arc stabilizer

Advances in manufacturing emphasize on the development of sustainable and green manufacturing processes. Welding is a popular manufacturing process practiced worldwide. The paper presented here describes a new covered electrode for a shielded metal arc welding (SMAW) process wherein nano-sized calcium titanate (CaTiO3) powder was used as an arc stabilizer, replacing the conventional micro sized CaTiO3 in the flux. The effect of this flux modification on the mass concentration and morphology of welding fume particulates was systematically investigated. The mass concentration of coarse, fine and sub-micron sized fume particulates was measured by segregating the fumes in a four-stage personal cascade impactor. The particle mass distribution was estimated from the mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of the fume particulates. The morphology of fumes at each impactor stage was analysed using scanning electron microscopy and its count median diameter (CMD) was determined. The results indicated as much as 48 % reduction in total fumes and 54 % reduction in the breathing zone concentration of fumes when the entire CaTiO3 in the electrode flux was substituted with nano-CaTiO3. Morphological analysis indicated that a large fraction of the fumes from the conventional electrode were polydispersed particles, while the new electrodes predominantly contained monodispersed particles which have a relatively faster rate of removal from the lungs. Overall, the present work indicated that introducing nano sized CaTiO3 as an arc stabilizer to the flux covering of SMAW electrode could not only reduce the hazardous fume emissions but also reduce its biological activity and toxicity, thus making the process more sustainable and environment friendly.