Neutralizing antibodies after nebulized phage therapy in cystic fibrosis patients.

BACKGROUND: Cystic fibrosis (CF) patients are prone to recurrent multi-drug-resistant (MDR) bacterial lung infections. Under this scenario, phage therapy has been proposed as a promising tool. However, the limited number of reported cases hampers the understanding of clinical outcomes. Anti-phage immune responses have often been overlooked and only described following invasive routes of administration. METHODS: Three monophage treatments against Staphylococcus aureus and/or Pseudomonas aeruginosa lung infections were conducted in cystic fibrosis patients. In-house phage preparations were nebulized over 10 days with standard-of-care antibiotics. Clinical indicators, bacterial counts, phage and antibiotic susceptibility, phage detection, and immune responses were monitored. FINDINGS: Bacterial load was reduced by 3-6 log in two of the treatments. No adverse events were described. Phages remained in sputum up to 33 days after completion of the treatment. In all cases, phage-neutralizing antibodies were detected in serum from 10 to 42 days post treatment, with this being the first report of anti-phage antibodies after nebulized therapy. CONCLUSIONS: Nebulized phage therapy reduced bacterial load, improving quality of life even without bacterial eradication. The emergence of antibodies emphasizes the importance of long-term monitoring to better understand clinical outcomes. These findings encourage the use of personalized monophage therapies in contrast to ready-to-use cocktails, which might induce undesirable antibody generation. FUNDING: This study was supported by the Spanish Ministry of Science, Innovation and Universities; Generalitat Valenciana; and a crowdfunding in collaboration with the Spanish Cystic Fibrosis Foundation.

Pulmonary delivery of icariin-phospholipid complex prolongs lung retention and improves therapeutic efficacy in mice with acute lung injury/ARDS.

Icariin has been shown the promising therapeutic potential to treat inflammatory airway diseases, yet its poor lung distribution and retention restrict the clinical applications. To this end, this work aimed to prepare an icariin-phospholipid complex (IPC) formulation for sustained nebulization delivery that enabled excellent inhalability, improved lung exposure and prolonged duration of action. Icariin was found to react with soybean phospholipid to form supramolecular IPC, which was able to self-assemble into nanoparticle suspension. The suspension was stable during steam sterilization and nebulization processes, and its aerosols generated by a commercial nebulizer exhibited excellent aerodynamic properties and delivery efficiency. In vitro studies showed that the formation of complex sustained drug release, enhanced lung affinity and slowed lung clearance. The drug distribution in lung epithelial lining fluid (ELF) also demonstrated in vivo sustained release after intratracheal administration to mice. In addition, compared to free icariin, IPC improved the drug exposure to lung tissues and immune cells in the ELF by 4.61-fold and 39.5-fold, respectively. This resulted in improved and prolonged local anti-inflammatory effects up to 24 h in mice with lipopolysaccharide (LPS)-induced acute lung injury. Moreover, IPC improved survival rate of mice with acute respiratory distress syndrome (ARDS). Overall, the present phospholipid complex represented a promising formulation of icariin for the treatment of acute lung injury/ARDS by nebulization delivery.

Comparison of Forward-Leaning and Fowler Position: Effects on Vital Signs, Pain, and Anxiety Scores in Children With Asthma Exacerbations.

BACKGROUND: It is essential to relieve bronchospasm or specific asthma symptoms by administering immediate inhaler treatment during an asthma exacerbation. The present study compared the effect of Fowler position and forward-leaning positions during nebulization on heart rate, SpO2 , breathing frequency, pain, and anxiety levels in children experiencing asthma exacerbations. METHODS: The data originated from a randomized trial that compared 86 participants (study group n = 43, control group n = 43) who presented to the pediatric emergency department with asthma exacerbations between October 2019-February 2020. The subjects were administered nebulization 3 times, during which the study group was placed in the forward-leaning position and the control group in the routine Fowler position. The subjects provided information on chest pain and anxiety levels before and after nebulization, and heart rate, SpO2 , and breathing frequency were measured before and after each nebulization. RESULTS: The difference in the mean SpO2 measured at admission and after the third nebulization was significantly higher (3.2 ± 1.5% vs 2.3 ± 1.9%, P = .01); the difference in the mean breathing frequency was considerably higher (-6.0 ± 1.7 breaths/min vs -3.2 ± 1.8 breaths/min, P < .001), and the difference in the mean pain scores was significantly higher (-3.3 ± 2.5 vs -2.0 ± 2.3, P = .02) in the study group than in the control group. In addition, after the third nebulization, the breathing frequency (22.8 ± 2.8 breaths/min vs 24.2 ± 2.7 breaths/min, P = .02) and pain score of the study group were lower (0.8 ± 1.3 vs 1.5 ± 1.5, P = .01). There was no difference in the mean heart rate (20.6 ± 16.2 beats/min vs 20.0 ± 15.4 beats/min, P = .85) and anxiety levels (-2.0 ± 2.2 vs -1.9 ± 2.2, P = .90) between the groups. CONCLUSIONS: Placing children in a forward-leaning position during nebulization was effective in improving SpO2 and reducing breathing frequency and chest pain. The forward-leaning position implemented during nebulization is a non-pharmacologic method that supports recovery in children with asthma exacerbations.

Clinical analysis of colistin sulfate in the treatment of pneumonia caused by carbapenem-resistant Gram-negative bacteria.

BACKGROUND: Multidrug-resistant Gram-negative bacteria, exacerbated by excessive use of antimicrobials and immunosuppressants, are a major health threat. AIM: To study the clinical efficacy and safety of colistin sulfate in the treatment of carbapenem-resistant Gram-negative bacilli-induced pneumonia, and to provide theoretical reference for clinical diagnosis and treatment. METHODS: This retrospective analysis involved 54 patients with Gram-negative bacilli pneumonia admitted to intensive care unit of The General Hospital of the Northern Theater Command of the People's Liberation Army of China from August 2020 to June 2022. After bacteriological culture, the patients' airway secretions were collected to confirm the presence of Gram-negative bacilli. The patients were divided into the experimental and control groups according to the medication used. The research group consisted of 28 patients who received polymyxin sulfate combined with other drugs through intravenous, nebulization, or intravenous combined with nebulization, with a daily dosage of 1.5-3.0 million units. The control group consisted of 26 patients who received standard dosages of other antibiotics (including sulbactam sodium for injection, cefoperazone sodium sulbactam for injection, tigecycline, meropenem, or vaborbactam). RESULTS: Of the 28 patients included in the research group, 26 patients showed improvement, treatment was ineffective for two patients, and one patient died, with the treatment efficacy rate of 92.82%. Of the 26 patients in the control group, 18 patients improved, treatment was ineffective for eight patients, and two patients died, with the treatment efficacy rate of 54.9%; significant difference was observed between the two groups (P < 0.05). The levels of white blood cell (WBC), procalcitonin (PCT), and C-reactive protein (CRP) in both groups were significantly lower after treatment than before treatment (P < 0.05), and the levels of WBC, PCT, and CRP in the research group were significantly lower than those in the control group (P < 0.05). Compared with before treatment, there were no significant changes in aspartate aminotransferase, creatinine, and glomerular filtration rate in both groups, while total bilirubin and alanine aminotransferase decreased after treatment (P < 0.05) with no difference between the groups. In patients with good clinical outcomes, the sequential organ failure assessment (SOFA) score was low when treated with inhaled polymyxin sulfate, and specific antibiotic treatment did not improve the outcome. Sepsis and septic shock as well as a low SOFA score were independent factors associated with good clinical outcomes. CONCLUSION: Polymyxin sulfate has a significant effect on the treatment of patients with multiple drug-resistant Gram-negative bacilli pneumonia and other infections in the lungs and is safe and reliable. Moreover, the administration route of low-dose intravenous injection combined with nebulization shows better therapeutic effects and lower adverse reactions, providing new ideas for clinical administration.

Nebulized Inhalation of Peptide-Modified DNA Origami To Alleviate Acute Lung Injury.

Acute lung injury (ALI) is a severe inflammatory lung disease, with high mortality rates. Early intervention by reactive oxygen species (ROS) scavengers could reduce ROS accumulation, break the inflammation expansion chain in alveolar macrophages (AMs), and avoid irreversible damage to alveolar epithelial and endothelial cells. Here, we reported cell-penetrating R9 peptide-modified triangular DNA origami nanostructures (tDONs-R9) as a novel nebulizable drug that could reach the deep alveolar regions and exhibit an enhanced uptake preference of macrophages. tDONs-R9 suppressed the expression of pro-inflammatory cytokines and drove polarization toward the anti-inflammatory M2 phenotype in macrophages. In the LPS-induced ALI mouse model, treatment with nebulized tDONs-R9 alleviated the overwhelming ROS, pro-inflammatory cytokines, and neutrophil infiltration in the lungs. Our study demonstrates that tDONs-R9 has the potential for ALI treatment, and the programmable DNA origami nanostructures provide a new drug delivery platform for pulmonary disease treatment with high delivery efficiency and biosecurity.

Prevalence and Management of Chronic Obstructive Pulmonary Disease in the Gulf Countries with a Focus on Inhaled Pharmacotherapy.

Background: Chronic obstructive pulmonary disease (COPD) is a preventable, progressive disease and the third leading cause of death worldwide. The epidemiological data of COPD from Gulf countries are very limited, as it remains underdiagnosed and underestimated. Risk factors for COPD include tobacco cigarette smoking, water pipe smoking (Shisha), exposure to air pollutants, occupational dusts, fumes, and chemicals. Inadequate treatment of COPD leads to worsening of disease. The 2024 GOLD guidelines recommend use of inhaled bronchodilators, corticosteroids, and adjunct therapies for treatment and management of COPD patients based on an individual assessment of the severity of symptoms and risk of exacerbations. This article reviews COPD pharmacotherapy in the Gulf countries and explores the role of nebulization in the management of COPD in this region. Methods: To review the COPD pharmacotherapy in the Gulf Countries, literature search was conducted using PubMed, Medline, Cochrane Systematic Reviews, and Google Scholar databases (before December 2022), using search terms such as COPD, nebulization, inhalers/inhalation, aerosols, and Gulf countries. Relevant articles from the reference list of identified studies were reviewed. Consensus statements, expert opinion, and other published review articles were included. Results: In the Gulf countries, pressurized metered-dose inhalers (pMDIs), dry powder inhalers (DPIs), soft mist inhalers, and nebulizers are used for drug delivery to COPD patients. pMDIs and DPIs are most prone to errors in technique and other common device handling errors. Nebulization is another mode of inhalation drug delivery, which is beneficial in certain patient populations such as the elderly and patients with cognitive impairment, motor or neuromuscular disorders, and other comorbidities. Conclusion: There is no major difference between Gulf countries and rest of the world in the approach to management of COPD. Nebulizers should be considered for patients who have difficulties in accessing or using MDIs and DPIs, irrespective of geographical location.

Setup of Aerosol Delivery System to Prevent Measles Virus Infection in Nonhuman Primate Model.

Measles virus is one of the most contagious airborne human viruses which keeps causing outbreaks in numerous countries over the world despite the existence of an efficient vaccine. Fusion inhibitory lipopeptides were shown to inhibit viral entry into target cells, and their adequate administration into the respiratory tract may provide a novel preventive approach against airborne infections. Aerosol delivery presents the best administration route to deliver such preventive compounds to the upper and lower respiratory tract. This approach offers a conceptually new strategy to protect the population at risk against infection by respiratory viruses, including measles. It is a noninvasive needle-free approach, which may be used when antiviral protection is required, without any medical assistance. In this chapter, we describe the nebulization approach of lipopeptide compounds in nonhuman primates and the subsequent measles virus challenge.

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

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

Post-Tracheostomy Steroid Nebulization: A Retrospective Analysis on Postoperative Complications.

The primary objective of this research was to meticulously evaluate the therapeutic potential of steroid nebulization, administered over a 2-week period post-tracheostomy, in attenuating postoperative complications with a concentrated emphasis on tracheal stenosis. The study spanned three years, commencing in 2019 and concluding in 2022, examining a patient cohort of 400 individuals. Utilizing a retrospective cohort methodology, the participants were systematically stratified into two cohorts: those subjected to steroid nebulization (n = 200) and a control group (n = 200). Adverse outcomes were bifurcated into minor complications, which encompass stomal infections and inflammations, and major complications, which include bleeding, tracheoesophageal fistula, and tracheal stenosis. These complications were evaluated at distinct post-operative junctures: 1 week, 1 month, 3 months, and 6 months. The primary outcome was deduced through a rigorous multivariate logistic regression model, incorporating variables such as age, sex, and the diagnosis of chronic obstructive pulmonary disease (COPD). Analytical data unveiled that the cohort administered with steroid nebulization manifested a statistically significant diminution in the incidence of complications when juxtaposed with the control group (25 vs. 38%). Predominantly, the incidence of tracheal stenosis was discernibly lower in the steroid nebulization group (10 vs. 22%). The multivariate analytical framework further corroborated the pivotal role of steroid nebulization in substantially reducing the propensity for tracheal stenosis. The therapeutic intervention of steroid nebulization in the aftermath of a tracheostomy procedure presents a commendable avenue in curtailing major complications, with an acute focus on tracheal stenosis. To fortify these preliminary findings, it is quintessential to undertake more exhaustive studies, such as randomized controlled trials, to ascertain the optimal regimen concerning nebulization's timing, dosage, and duration.

Investigating the effectiveness of liposome-bacteriophage nanocomplex in killing Staphylococcus aureus using epithelial cell coculture models.

Host cell invasion with strong antibiotics evading is a major feature of respiratory Staphylococcus aureus infections with severe recurrence. Bacteriophage (phage) therapy and design of liposomal phage to target intracellular pathogens have been described recently. The practicality for pulmonary delivery of liposomal phage, and how formulation compositions affecting the aerosolization and intracellular bacterial killing remain unexplored. In the present study, three commonly used phospholipids (SPC, EPC, and HSPC) were selected to investigate their ability for phage K nebulization and intracellular therapy in the form of liposome-phage nanocomplexes. The three lipid nanocarriers showed protection on phage K upon mesh nebulization and the pulmonary deposition efficiency was influenced by the lipid used. Moreover, the intracellular bacterial killing was strongly depended on the lipid types, where EPC-phage exhibited the best killing performance with no relapsing. Phage K with the aid of EPC liposomes was also observed to manage the tissue infection in a 3D spheroid model more effectively than other groups. Altogether, this novel EPC liposome-phage nanocomplex can be a promising formulation approach that enables inhalable phage to manage respiratory infections caused by bacteria strongly associated with human epithelial cells.

Hyaluronic acid modified nanocarriers for aerosolized delivery of verteporfin in the treatment of acute lung injury.

Verteporfin (VER), a photosensitizer used in macular degeneration therapy, has shown promise in controlling macrophage polarization and alleviating inflammation in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). However, its hydrophobicity, limited bioavailability, and side effects hinder its therapeutic potential. In this study, we aimed to enhance the therapeutic potential of VER through pulmonary nebulized drug delivery for ALI/ARDS treatment. We combined hydrophilic hyaluronic acid (HA) with an oil-in-water system containing a poly(lactic acid-co-glycolic acid) (PLGA) copolymer of VER to synthesize HA@PLGA-VER (PHV) nanoparticles with favorable surface characteristics to improve the bioavailability and targeting ability of VER. PHV possesses suitable electrical properties, a narrow size distribution (approximately 200 nm), and favorable stability. In vitro and in vivo studies demonstrated the excellent biocompatibility, safety, and anti-inflammatory responses of the PHV by suppressing M1 macrophage polarization while inducing M2 polarization. The in vivo experiments indicated that the treatment with aerosolized nano-VER (PHV) allowed more drugs to accumulate and penetrate into the lungs, improved the pulmonary function and attenuated lung injury, and mortality of ALI mice, achieving improved therapeutic outcomes. These findings highlight the potential of PHV as a promising delivery system via nebulization for enhancing the therapeutic effects of VER in ALI/ARDS.

Simultaneous and on-line detection of organic and heavy metal components in water using a novel nebulization-assisted injection plasma ionization triple quadruple mass spectrometry instrument.

BACKGROUND: The global release of organic and heavy metal components into natural water bodies is a major concern for the environment and human health. The assessment of water quality relies on analyzing organic and heavy metal components qualitatively and quantitatively. Real-time identification of organic and metal components in water systems requires different analytical techniques due to varying measurement requirements. Thus, on-line detecting both organic compounds and heavy metals in ambient water systems simultaneously using a single instrumentation setup presents a significant challenge. RESULTS: In this study, an analytical technique of nebulization-assisted injection plasma ionization mass spectrometry (NI-PIMS) was developed. This novel method enables the simultaneous detection of heavy metals and organic compounds in water system with high sensitivity, which has been demonstrated by the limit of quantification (LOQ) values below 1.0 µg/L for the three sterols (Enrofloxacin, ciprofloxacin, and clenbuterol) and three heavy metals (Pb, Ba, and Cd). Moreover, the method was successfully applied to rapidly analyze real water samples from urban and rural areas in China. The analytical results are available in less than 0.5 min, and only a few microliters of sample are required for each analysis. SIGNIFICANCE AND NOVELTY: As far as we know, this is the first report of on-line simultaneous analysis of organic compounds and heavy metals in a water system using a single mass spectrometry instrument. Compared to traditional methods, NI-PIMS demonstrates higher efficiency, sensitivity, no or lower sample preparation, and less sample consumption. The advancement and widespread use of this technology are expected to enhance the effectiveness of mass spectrometers, broaden the applications, and play an important role in complex sample analysis in fields such as atmospheric science, environmental science, and earth science.

Efficacy of the posterior nasal nerve resection combined with hormone transnasal nebulization on difficult-to-treat rhinosinusitis: a retrospective analysis.

OBJECTIVE: A retrospective analysis was performed to explore the clinical effect of the Posterior Nasal Nerve (PNN) resection combined with hormone transnasal nebulization on Difficult-to-Treat Rhinosinusitis (DTRS). METHODS: A total of 120 DTRS patients were selected and divided into a control group (n = 60) and a study group (n = 60) according to different treatments. The control group patients were treated via PNN resection, followed by normal saline transnasal nebulization; the study group patients were given PNN resection and then treated with budesonide suspension transnasal nebulization. Subsequently, the comparison was performed between the two groups in terms of (1) Clinical baseline characteristics; (2) Sino-nasal Outcome Test (SNOT)-22 scores before treatment and after 3-months, 6-months and 12-months of treatment; (3) Lund-MacKay scores before treatment and after 10, 30, 90, and 180 days of treatment; (4) Incidence of adverse reactions during treatment. RESULTS: There was no significant difference in SNOT-22 or Lund-Kennedy scores between the two groups before treatment (p > 0.05). After treatment, the SNOT-22 and Lund-Kennedy scores of the control and the study groups were decreased, and compared with the control group, the SNOT-22 and Lund-Kennedy scores in the study group improved more significantly (p < 0.05). In addition, the study group and the control group presented with 1 and 4 cases of nasal adhesion, 2 and 3 cases of epistaxis, 1 and 4 cases of sinus orifice obstruction, 1 and 3 cases of lacrimal duct injuries, respectively. The incidence of adverse reactions in the study group was significantly lower than that in the control group (8.3% vs. 23.3%) (p < 0.05). CONCLUSION: PNN resection combined with hormone transnasal nebulization treatment can improve the symptoms and quality of life of DTRS patients, with good clinical efficacy but few adverse reactions. Therefore, such combination treatment deserves a promotion and application clinically. LEVEL OF EVIDENCE: Level 3.

Nebulized Versus Intravenously Administered Dexmedetomidine for Obtunding Hemodynamic Responses to Laryngoscopy and Tracheal Intubation: A Randomized Double-Blind Comparative Study.

Introduction Intravenous dexmedetomidine is known to cause major adverse effects such as bradycardia, hypotension, cardiac arrhythmias, and heart block when used as premedication for attenuation of the laryngoscopy and intubation response, limiting its routine use. Thus, it is important to study other routes of administration of dexmedetomidine. Objectives To compare the hemodynamic response and sedation score between intravenous and nebulized dexmedetomidine as premedication for the attenuation of the laryngoscopy and intubation response. Materials and methods In this study, 60 patients fulfilling inclusion criteria undergoing surgeries under general anesthesia (ASA Grade I and II) were randomly allocated into two groups of 30 patients each. Group IV received intravenous 1 mcg/kg dexmedetomidine in 100 mL normal saline, and Group IN received nebulization with 1 mcg/kg dexmedetomidine diluted to a total volume of 5 cc of normal saline, 30 minutes prior to the induction of general anesthesia. Sedation scores were calculated using the Ramsay sedation score at 20 minutes after the administration of the drug; patients were induced by the standard protocol, and laryngoscopy was performed. Vitals were recorded before the administration of the drug and after intubation at stipulated time intervals. Results The median heart rate becomes significantly lower at 15 minutes (70 vs. 76.5) and 20 minutes (66 vs. 76) after induction among Group IV as compared to Group IN. The median systolic blood pressure was significantly lower at 20 minutes in Group IV (110 mmHg) than in Group IN (119 mmHg). The median diastolic blood pressure was significantly lower at 10 minutes (76 vs. 79), 15 minutes (70 vs. 77), and 20 minutes (69 vs. 78.5) in Group IV than in Group IN. The median of mean arterial pressure was significantly lower at 15 minutes (84.8 vs. 91.5) and 20 minutes (83 vs. 92) in Group IV than in Group IN. A comparison of vitals after induction shows that the median heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure were significantly lower statistically among Group IV as compared to Group IN at 0, 1, 3, 5, 10, 15, and 30 minutes after induction (except for systolic blood pressure at 3 minutes). The median sedation score was lower in Group IN (0) than in Group IV (1); this difference is statistically significant. Conclusion The obtundation of hemodynamic responses following laryngoscopy and maintaining hemodynamics intraoperatively is statistically better with nebulized dexmedetomidine compared to intravenous dexmedetomidine.

Evaluating the photodynamic efficacy of nebulized curcumin-loaded liposomes prepared by thin-film hydration and dual centrifugation: In vitro and in ovo studies.

Lung cancer, one of the most common causes of high mortality worldwide, still lacks appropriate and convenient treatment options. Photodynamic therapy (PDT) has shown promising results against cancer, especially in recent years. However, pulmonary drug delivery of the predominantly hydrophobic photosensitizers still represents a significant obstacle. Nebulizing DPPC/Cholesterol liposomes loaded with the photosensitizer curcumin via a vibrating mesh nebulizer might overcome current restrictions. In this study, the liposomes were prepared by conventional thin-film hydration and two other methods based on dual centrifugation. The liposomes' physicochemical properties were determined before and after nebulization, showing that liposomes do not undergo any changes. However, morphological characterization of the differently prepared liposomes revealed structural differences between the methods in terms of lamellarity. Internalization of curcumin in lung adenocarcinoma (A549) cells was visualized and quantified. The generation of reactive oxygen species because of the photoreaction was also proven. The photodynamic efficacy of the liposomal formulations was tested against A549 cells. They revealed different phototoxic responses at different radiant exposures. Furthermore, the photodynamic efficacy was investigated after nebulizing curcumin-loaded liposomes onto xenografted tumors on the CAM, followed by irradiation, and evaluated using positron emission tomography/computed tomography and histological analysis. A decrease in tumor metabolism could be observed. Based on the efficacy of curcumin-loaded liposomes in 2D and 3D models, liposomes, especially with prior film formation, can be considered a promising approach for PDT against lung cancer.

Novel inhalation therapy in pulmonary fibrosis: principles, applications and prospects.

Pulmonary fibrosis (PF) threatens millions of people worldwide with its irreversible progression. Although the underlying pathogenesis of PF is not fully understood, there is evidence to suggest that the disease can be blocked at various stages. Inhalation therapy has been applied for lung diseases such as asthma and chronic obstructive pulmonary disease, and its application for treating PF is currently under consideration. New techniques in inhalation therapy, such as the application of microparticles and nanoparticles, traditional Chinese medicine monomers, gene therapy, inhibitors, or agonists of signaling pathways, extracellular vesicle interventions, and other specific drugs, are effective in treating PF. However, the safety and effectiveness of these therapeutic techniques are influenced by the properties of inhaled particles, biological and pathological barriers, and the type of inhalation device used. This review provides a comprehensive overview of the pharmacological, pharmaceutical, technical, preclinical, and clinical experimental aspects of novel inhalation therapy for treating PF and focus on therapeutic methods that significantly improve existing technologies or expand the range of drugs that can be administered via inhalation. Although inhalation therapy for PF has some limitations, the advantages are significant, and further research and innovation about new inhalation techniques and drugs are encouraged.

The effect of various inhaled asthma medications on the color stability of paediatric dental restorative materials.

BACKGROUND: The purpose of the study is to analyse the effects of different inhaled asthma medications (IAMs) on the color change of dental restorative materials (DRMs). METHODS: In total, 192 samples were taken from six different DRMs: [Filtek Z550 (nanohybrid composite), Fusio Liquid Dentin (Self-adhering flowable composite), Filtek Ultimate (nanofilled flowable composite), Dyract XP (compomer), Fuji II LC (resin-modified glass ionomer), Fuji IX Fast (self-cured-packable glass ionomer), (n = 32)]. After the initial color values (CIELab) of DRMs were measured by using a spectrophotometer, each sample was exposed to the same IAMs via nebulizer according to the four different inhaled therapies and measurements were repeated on the 7th & 21st days. RESULTS: In all IAM groups, DRM with the least amount of ΔE was nanohybrid composite, while the highest ΔE was found in Fuji II LC. Among all experimental groups, only Fuji II LC which was administered the combined medication, exceeded the clinically unacceptable threshold (ΔE = 3.3) on 7th & 21st days. CONCLUSIONS: Consequently, important factors affecting the susceptibility to color stability are the type of IAMs, the administration time-dosage, and the type of DRMs.

Intrapulmonary and Systemic Pharmacokinetics of Colistin Following Nebulization of Low-Dose Colistimethate Sodium in Patients with Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant Acinetobacter baumannii.

Colistimethate sodium (CMS) nebulization is associated with reduced systemic toxicity compared to intravenous injection, with potentially enhanced clinical efficacy. This study aimed to assess the pharmacokinetic (PK) properties of colistin during low-dose CMS nebulization in patients with ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii. A nonlinear mixed-effects modeling approach was applied to develop population PK models for colistin in both epithelial lining fluid (ELF) and plasma. Twenty patients participated, and 80 ELF and 100 plasma samples were used for model development. Median colistin concentrations measured in ELF were 614-fold, 408-fold, and 250-fold higher than in plasma at 1, 3, and 5 h, respectively. Time courses in both ELF and plasma were best described by a one-compartment model with a Weibull absorption process. When the final model was simulated, the maximum free concentration and area under the free colistin concentration-time curve at steady state over 24 h in the plasma were approximately 1/90 and 1/50 of the corresponding values in ELF at steady state, respectively. For an A. baumannii MIC of 1 mg/L, inhaling 75 mg of CMS at 6 h intervals was deemed appropriate, with dose adjustments needed for MICs exceeding 2 mg/L. Using a nebulizer for CMS resulted in a notably higher exposure of colistin in the ELF than plasma, indicating the potential of nebulization to reduce systemic toxicity while effectively treating VAP.

Dataset on exposure conditions to Fe2O3 and SiO2 colloidal suspension and airborne particulate matter (PM) suspensions: crude NIST1648a and with reduced content of organic matter, LAp120.

Particulate matter (PM) present in the air pollution increases morbidity and mortality due to several reasons. The dataset presents a comparative analysis of nebulization process of Fe2O3 and SiO2 nanoparticles or crude PM (NIST1648a) and that with reduced content of organic matter (LAp120). Nebulization tests were carried out to determine concentrations of nanoparticle and PM suspensions, in order to create an atmosphere with a concentration of PM particles about 1000 µg/m3 of air in the exposure chambers. It is important to properly recreate environmental conditions during further research on animals. The absorbance spectrum of the suspensions of the tested materials was measured in the range of 300-700 nm. The changes in the absorbance of these suspensions depending on the concentration after their passage through the nebulizers were examined. Based on the absorbance, it was determined to what extent the suspensions are passed out and dispersed by the nebulizers. The operating mode of the nebulizers and the concentration of suspensions were determined in order to establish the optimal exposure conditions and the microclimate of the chambers for further studies with mice. The dataset can help in optimization of nebulization process for all researchers exploring the further issue of the influence of the air pollution on the broadly understood animal functions, behavioral parameters and biochemical aspects.