Journal of Aerosol Medicine and Pulmonary Drug Delivery最新文献

{"title":"Development of Exclusive and Efficient Intranasal or Pulmonary Dosing Methods for a Dry Powder Tuberculosis Vaccine for Use in Nonhuman Primates.","authors":"John Z Chen, Scott Tavernini, Maximilian Aisenstat, Kelvin Duong, Hui Wang, Joseph McCollum, Wynton D McClary, Alana Gerhardt, Philip J Kuehl, Andrew R Martin, Reinhard Vehring, Christopher B Fox","doi":"10.1177/19412711251383716","DOIUrl":"https://doi.org/10.1177/19412711251383716","url":null,"abstract":"<p><p><b><i>Background:</i></b> In spite of efforts to eradicate tuberculosis (TB), TB remains the deadliest infectious disease in the world; there is an urgent need for a thermostable, noninvasive TB vaccine suitable for distribution in the developing world. Spray-dried versions of a clinical-stage TB vaccine, ID93 + GLA-SE, are currently undergoing testing in baboons in both pulmonary and intranasal versions. We developed manufacturing processes and delivery systems to achieve delivery of each version to its intended site of action while avoiding off-target deposition. <b><i>Methods:</i></b> Pulmonary ID93 + GLA-SE was manufactured in a custom research-scale spray dryer. Delivery efficiency using a custom intratracheal insufflator was measured gravimetrically, and aerodynamic performance was evaluated via cascade impaction. Intranasal ID93 + GLA-SE was manufactured in a pilot-scale spray dryer. <i>In vitro</i> regional deposition in the Alberta Idealized Nasal Inlet, measured by LC-MS/MS, was used as a surrogate for aerodynamic performance; total deposition was used to calculate a total delivered dose. For both powders, ID93 antigen content was assessed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and GLA-SE adjuvant content was assessed via HPLC. <b><i>Results:</i></b> No substantial processing losses of the antigen or adjuvant were observed after spray drying in either formulation. For the pulmonary powder, the emitted dose exiting the endotracheal tube across three tube sizes ranged from 15.9% to 21.4% of the nominal dose; for the 8 mm tube size, the emitted dose mass median aerodynamic diameter was 5.3 µm, which was deemed suitable for pulmonary administration. For the intranasal powder, the delivered dose was 88% ± 2% of nominal, and <i>in vitro</i> deposition in the posterior nasal cavity was 63% ± 10% of the emitted dose, with minimal anticipated lung deposition. <b><i>Conclusions:</i></b> Pulmonary and intranasal spray-dried ID93 + GLA-SE powders were successfully manufactured. The proposed dosing systems are expected to achieve exclusive pulmonary or intranasal delivery to nonhuman primates while requiring only a moderate amount of powder.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic Analysis of Compounds Instilled into the Mouse Lung: Study with <i>In Vivo</i> Electron Spin Resonance Spectroscopy and Nitroxyl Spin Probes as Model Drugs.","authors":"Jin-Yi Han, Keizo Takeshita, Shoko Okazaki, Hideo Utsumi","doi":"10.1177/19412711251379678","DOIUrl":"https://doi.org/10.1177/19412711251379678","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Detailed understanding of the absorption mechanisms of compounds in the lungs is important for developing effective systems for the pulmonary administration of drugs. This study analyzed the pharmacokinetics of model compounds instilled into the mouse lungs using <i>in vivo</i> electron spin resonance (ESR) spectroscopy. <b><i>Methods:</i></b> An aqueous solution of a nitroxyl probe with cationic, anionic, or neutral groups was instilled into the lungs of healthy mice at high concentrations as model drugs, and the behavior of the probes was assessed using concentration-dependent changes in the linewidths of ESR signals obtained in live mice. <b><i>Results:</i></b> When solutions of nitroxyl probes at high concentrations, which produce broad ESR signals, were instilled into the mouse lungs, sharp ESR signals originating from diluted probes were superimposed onto broad signals. Broad signals decreased at various rates for all probes depending on their lipophilicity. Sharp signals for neutral probe and anionic probe immediately increased after instillation and then decreased. Sharp signals for cationic probe with a quaternary ammonium group continued to increase after instillation. Pharmacokinetic analysis of the blood concentrations of these probes suggests that the probes are distributed to lung tissues in addition to the blood. The concentration dependence of the initial velocity of broad signal decay suggests the possibility that the transfer of charged probes from the alveolar space to the bloodstream may be mediated by transporters, whereas a neutral probe may be transferred via passive diffusion. <b><i>Conclusion:</i></b> The differences in pharmacokinetic behavior in lungs could be examined <i>in vivo</i> among model compounds with different charge states. <i>In vivo</i> ESR spectroscopy is a powerful tool for the <i>in vivo</i> analysis of pulmonary pharmacokinetics, in combination with nitroxyl probes as model drugs.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knowledge of Nurses and Primary Care Physicians on Inhaled Therapy Devices and Techniques.","authors":"Francisco Javier Plaza-Zamora, Valentín López-Carrasco, Jordi Giner-Donaire, Jaime Gonzalvez-Rey, María Del Carmen Mata-Hernández, Marta Villanueva Pérez","doi":"10.1177/19412711251380101","DOIUrl":"https://doi.org/10.1177/19412711251380101","url":null,"abstract":"<p><p><b><i>Background:</i></b> We aimed to assess the knowledge of health care professionals regarding inhaled therapy devices and techniques and to evaluate the effectiveness of a targeted educational intervention. <b><i>Methods:</i></b> An educational program designed to update the knowledge and improve the technical skills of these professionals in the use of different types of inhalers was developed. Before and after each training session, we applied an <i>ad hoc</i> questionnaire that consisted of 15 multiple-choice questions on inhaled therapy grouped into three sections, including knowledge about devices used for inhaled therapy, knowledge about inhaler techniques, and knowledge about adherence to inhaled therapy, as well as the Test of the Adherence to Inhalers. The questionnaire also included a summary question. We calculated the mean score and the standard deviation for the pre- and postevaluations, compared the mean scores using Student's <i>t-test,</i> and evaluated the relevance of the changes using Cohen's <i>d</i>. <b><i>Results:</i></b> During the 23 meetings held throughout Spain, 267 participants completed the pretraining questionnaire, including 105 primary care physicians, 90 nurses of specialized care, 41 nurses working in primary care, and 31 health care professionals of various origins. Overall, the mean (SD) total score (i.e., number of correct answers out of a maximum of 15; range 0-15) significantly increased from 8.99 (2.26) to 11.46 (2.50) points, for a mean pre-post difference of 2.5 (<i>p</i> < 0.001). Notable issues included the misidentification of device types and confusion between inhalation techniques for pressurized metered-dose inhalers and dry powder inhalers. The mean total scores significantly increased across the three main specialties, with large effect sizes in all cases. <b><i>Conclusion:</i></b> Our study suggests that both primary care physicians and nurses have relevant gaps in knowledge- and technique-related issues regarding the use of inhalation devices that could be improved using a brief educational intervention.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clofazimine Inhalation Suspension: A Novel Formulation for the Treatment of Pulmonary Nontuberculous Mycobacterial Disease.","authors":"Wassim H Fares, Burkhard Blank, Michael Castagna, Thomas Hofmann","doi":"10.1177/19412711251370275","DOIUrl":"https://doi.org/10.1177/19412711251370275","url":null,"abstract":"<p><p><b><i>Background:</i></b> Oral administration of clofazimine, an antimicrobial agent with demonstrated <i>in vitro</i> efficacy against nontuberculous mycobacteria (NTM), including <i>Mycobacterium avium</i> complex, requires high dosages to reach minimum inhibitory concentration in the lungs. Clofazimine Inhalation Suspension is a novel formulation designed to offer rapid, targeted drug delivery with prolonged half-life in lung tissues while minimizing systemic toxicities. The objective of this study was to evaluate the pharmacokinetic and safety profiles and proposed dosing regimen of Clofazimine Inhalation Suspension for adjuvant treatment of pulmonary NTM disease. <b><i>Methods:</i></b> A proposed dosing regimen consisting of 28 days of once-daily 4 mL Clofazimine Inhalation Suspension (nominal 80 mg clofazimine) via jet nebulizer followed by a 56-day drug-intake holiday was evaluated using: (1) a first-in-human phase 1 study examining safety, tolerability, and plasma pharmacokinetics of single and multiple ascending doses across 30-90 mg of clofazimine, (2) a physiology-based pharmacokinetic model establishing human equivalent dosing based on preclinical, and phase 1 human Clofazimine Inhalation Suspension data along with published oral clofazimine data and generated human lung pharmacokinetic estimates. <b><i>Results:</i></b> Human studies showed no safety issues at any dose. In healthy volunteers, treatment was well tolerated, with mild adverse events and no signs of systemic clofazimine deposition in the skin or sclera. Plasma drug levels are anticipated to remain below the previously established safe levels for oral clofazimine. <b><i>Discussion:</i></b> Clofazimine Inhalation Suspension demonstrated effective antimicrobial lung concentrations and achievable long-term coverage with potential for less systemic toxicity than oral clofazimine. This novel formulation is an alternative delivery strategy to oral ingestion for pulmonary NTM disease. Further evaluation in the phase 3 ICoN-1 global clinical trial is underway.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145175178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Letter:</i> Response to Comment on \"Association of Inhaled Corticosteroid Use With COVID-19 Severity and Hospitalization in Patients With and Without Respiratory Disease\".","authors":"Michal Leibovich, Bernice Oberman, Jacob Cohen, Tamar Strahl, Noga Yosef, Yael Reichenberg, Dekel Shlomi","doi":"10.1177/19412711251382846","DOIUrl":"https://doi.org/10.1177/19412711251382846","url":null,"abstract":"","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Richard William Fuller-The Clinical Scientist Behind the Development of Multiple Leading Inhaled Therapies for Asthma (b. June 29, 1953-d. 2024).","authors":"Anthony Hickey, Igor Gonda, Paul J Atkins","doi":"10.1177/19412711251374582","DOIUrl":"https://doi.org/10.1177/19412711251374582","url":null,"abstract":"","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Difference in Exposure and Tolerability when Comparing Intratracheal Instillation with Inhaled Delivery.","authors":"Mikael Brülls, Elin Holmedal, Ramon Hendrickx","doi":"10.1177/19412711251374845","DOIUrl":"https://doi.org/10.1177/19412711251374845","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> To investigate the impact of two different routes of administration on the lung and systemic exposure of drugs designed for local delivery to the lung. <b><i>Methods:</i></b> In our comparative studies, similar lung doses of three different drugs were administered to rodents by both intratracheal instillation and inhaled delivery. <b><i>Results:</i></b> An obvious but unexpected difference in the exposure was observed. Immediately after the dose, the initial plasma concentration was much higher whereas the initial fraction of the lung dose in the lung was clearly lower for the instillation compared with the inhaled delivery. There was also a difference in the tolerability for one of the drugs when the same lung dose was administered and the inhaled dose was, in contrast to the instilled dose, tolerated by the mice. <b><i>Conclusions:</i></b> A plausible explanation for the observed but contrary to expected difference is that the drugs leaked from the lung into the systemic circulation already during the instillation procedure due to its invasive nature.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-Participant Blinded Investigation into Internal Losses of Medication in Commercially Available Mixing Inlets: Testing Different Orally Inhaled Product Classes Following Pharmacopeial Methods.","authors":"Patrik U Andersson, Jim Clay, Mark Parry, Teresa Iley, Daryl L Roberts, Lois Slator, Mårten Svensson, Hlack Mohammed, Jolyon P Mitchell","doi":"10.1177/19412711251370473","DOIUrl":"https://doi.org/10.1177/19412711251370473","url":null,"abstract":"<p><p><b><i>Background:</i></b> The \"Miller\" design of mixing inlet (MI) enables a cascade impactor to operate at a constant flow rate while the orally inhaled product-on-test is evaluated at varying flow rates by controlling the flow of air via its side-arm. <b><i>Study Purpose:</i></b> As part of the European Pharmaceutical Aerosol Group (EPAG) Impactor subgroup, we report a cross-industry experimental investigation by five organizations to determine internal losses of different inhaler-generated aerosolized medications within commercially available MIs, focusing on pharmacopeial methods for product testing. <b><i>Methods:</i></b> Evaluations were undertaken of solution and suspension formulations delivered by pressurized metered dose inhalers (pMDIs), passive dry powder inhalers (DPIs), and compressed air-jet and vibrating mesh nebulizers. Four different apparatuses were evaluated at different constant air flow rates entering the MI side arm. The nebulizers were tested utilizing a variable adult flow profile generated by a breathing simulator. <b><i>Results:</i></b> Losses within the MI were generally <5%, expressed as a percentage of the delivered mass of active pharmaceutical ingredient (API) ex-inhaler. These losses were sufficiently small that they can in most cases be accommodated within the allowance of ±5% OIP label claim emitted mass/actuation in the pharmacopeial compendia for total internal losses for aerodynamic particle size distribution (APSD) determination. However, corresponding average losses were between 2.8% and 5.2% of the mass of API presented to the MI for the blister-based DPIs. APSD-derived measures were largely unaffected by the magnitude of pressurized air flow up to 60 L/min to the side-arm of the MI, except for the solution-formulated pMDI, where increasing flow rate was associated with reduced mass median aerodynamic diameter and increased geometric standard deviation, suggestive of a dependency related to ethanol co-solvent evaporation rate. <b><i>Conclusions:</i></b> MI loss evaluation should be considered an important part of method development to minimize internal losses of the aerosolized medication being sampled.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploratory Pharmacokinetic Study of Pegylated Interferon Alfa-2b Aerosolized Inhalation Administration.","authors":"Hongran Chu, Hanzhou Wu, Fenfang Zou, Yalin Yin","doi":"10.1177/19412711251370951","DOIUrl":"https://doi.org/10.1177/19412711251370951","url":null,"abstract":"<p><p><b><i>Objective:</i></b> This study aimed to compare the pharmacokinetics and tissue distribution of aerosolized pegylated interferon α-2b (PEG IFNα-2b) with standard interferon α-2b (IFNα-2b) in an animal model, paving the way for further investigation into their pharmacodynamics. <b><i>Methods:</i></b> Fifty-six Sprague Dawley rats were divided into 14 groups receiving either PEG IFNα-2b or standard IFNα-2b via aerosolized inhalation into the lower respiratory tract. Each group received a single dose of consistent concentration and volume. Pharmacokinetic parameters such as C_max, T_max, t_1/2, AUC_(0-t), and MRT_(0-t) were evaluated through blood samples and tissue dissection at specified time intervals post-administration. <b><i>Results:</i></b> Analysis revealed significantly higher AUC_(0-t) and MRT_(0-t) in the lungs, trachea, and bronchi of the PEG IFNα-2b group compared to the standard IFNα-2b group (<i>p</i> < 0.05), with minimal systemic exposure. <b><i>Conclusion:</i></b> Aerosolized PEG IFNα-2b demonstrated increased drug exposure and retention in the lower respiratory tract compared to standard IFNα-2b, suggesting potential therapeutic advantages such as reduced dosing frequency. Further studies are warranted to explore enhanced clinical outcomes.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Corrigendum to:</i> \"<i>In Silico</i> Modeling of Resistances and Dosimetry in Sarcoidosis Patients with Airway Disease\".","authors":"","doi":"10.1177/19412711251368806","DOIUrl":"https://doi.org/10.1177/19412711251368806","url":null,"abstract":"","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}