Journal of Aerosol Medicine and Pulmonary Drug Delivery最新文献

{"title":"Heterogenous Intrapulmonary Distribution of Aerosolized Model Compounds in Mice with Bleomycin-Induced Pulmonary Fibrosis.","authors":"Kohei Togami, Yukimune Kanehira, Yuki Yumita, Hiroaki Ozaki, Rui Wang, Hitoshi Tada, Sumio Chono","doi":"10.1089/jamp.2023.0002","DOIUrl":"10.1089/jamp.2023.0002","url":null,"abstract":"<p><p><b><i>Background:</i></b> A distinctive pathological feature of idiopathic pulmonary fibrosis (IPF) is the aberrant accumulation of extracellular matrix components in the alveoli in abnormal remodeling and reconstruction following scarring of the alveolar structure. The current antifibrotic agents used for IPF therapy frequently result in systemic side effects because these agents are distributed, through the blood, to many different tissues after oral administration. In contrast to oral administration, the intrapulmonary administration of aerosolized drugs is believed to be an efficient method for their direct delivery to the focus sites in the lungs. However, how fibrotic lesions alter the distribution of aerosolized drugs following intrapulmonary administration remains largely unknown. In this study, we evaluate the intrapulmonary distribution characteristics of aerosolized model compounds in mice with bleomycin-induced pulmonary fibrosis through imaging the organs and alveoli. <b><i>Methods:</i></b> Aerosolized model compounds were administered to mice with bleomycin-induced pulmonary fibrosis using a Liquid MicroSprayer^®. The intrapulmonary distribution characteristics of aerosolized model compounds were evaluated through several imaging techniques, including noninvasive lung imaging using X-ray computed tomography, <i>ex vivo</i> imaging using zoom fluorescence microscopy, frozen tissue section observation, and three-dimensional imaging with tissue-clearing treatment using confocal laser microscopy. <b><i>Results:</i></b> In fibrotic lungs, the aerosolized model compounds were heterogeneously distributed. In observations of frozen tissue sections, model compounds were observed only in the fibrotic foci near airless spaces called honeycombs. In three-dimensional imaging of cleared tissue from fibrotic lungs, the area of the model compound in the alveolar space was smaller than in healthy lungs. <b><i>Conclusion:</i></b> The intrapulmonary deposition of extracellular matrix associated with pulmonary fibrosis limits the intrapulmonary distribution of aerosolized drugs. The development of delivery systems for antifibrotic agents to improve the distribution characteristics in fibrotic foci is necessary for effective IPF therapy.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"289-299"},"PeriodicalIF":3.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41235513","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":"Acknowledgment of Reviewers 2023.","authors":"","doi":"10.1089/vid.2023.29001.ack","DOIUrl":"https://doi.org/10.1089/vid.2023.29001.ack","url":null,"abstract":"","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"18 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139296960","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":"Abstracts from The International Society for Aerosols in Medicine.","authors":"","doi":"10.1089/jamp.2023.ab02.abstracts","DOIUrl":"https://doi.org/10.1089/jamp.2023.ab02.abstracts","url":null,"abstract":"","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71412352","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":"Abstract Author Index <i>by abstract number</i>.","authors":"","doi":"10.1089/jamp.2023.ab02.index.abstracts","DOIUrl":"https://doi.org/10.1089/jamp.2023.ab02.index.abstracts","url":null,"abstract":"","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71412351","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":"Bioequivalence of Two Tiotropium Dry Powder Inhalers and the Utility of Realistic Impactor Testing.","authors":"Clarissa Gobetti,&nbsp;Sanjeeva Dissanayake,&nbsp;Jag Shur,&nbsp;William Ganley,&nbsp;Lucas Silva,&nbsp;Isam Salem,&nbsp;Omaima Najib,&nbsp;Usama Harb","doi":"10.1089/jamp.2022.0065","DOIUrl":"10.1089/jamp.2022.0065","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Inhaled antimuscarinics are a cornerstone of the management of chronic obstructive pulmonary disease. This article details a series of five pharmacokinetic (PK) studies comparing a generic tiotropium dry powder inhaler (DPI) to Spiriva HandiHaler, the realistic <i>in vitro</i> methods used to support those studies, and the related <i>in vitro</i>-<i>in vivo</i> correlations (IVIVCs). <b><i>Methods:</i></b> All five PK studies were of open-label, single-dose, crossover design with test and reference treatments administered to healthy subjects. Following unexpected results in the first three PK studies, a realistic impactor method was developed comprising an Oropharyngeal Consortium (OPC) mouth-throat and simulated inspiratory profiles in conjunction with a Next Generation Impactor (NGI). Mass fractions and the <i>in vitro</i> whole lung dose were estimated for the test product and Spiriva^® HandiHaler^® using this method, and IVIVCs derived. <b><i>Results:</i></b> Bioequivalence could not be demonstrated for C_max in the first three PK studies (test/reference ratios ranging from 83.1% to 131.8%), although was observed for AUC_t. Reanalysis of the corresponding biobatches with the realistic NGI method revealed <i>in vitro</i> ratios aligned with these PK data (in contrast to the compendial NGI data) and thus inadvertent selection of \"mismatched\" biobatches. Two further PK studies were undertaken, supported by the realistic NGI method. With the comparison of test and reference products similarly positioned within their respective product performance distributions, bioequivalence was confirmed in both studies. IVIVCs based on mass fractions as per the realistic NGI method were robust and highly predictive of PK outcomes. <b><i>Conclusions:</i></b> The test tiotropium DPI and Spiriva HandiHaler were bioequivalent when equitable biobatch comparisons, based on realistic NGI testing, were performed. The observations from this program support the utility of realistic test methods for inhaled product development.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"257-267"},"PeriodicalIF":3.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9686699","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":"Inhalation Pharmacodynamics.","authors":"Ronald K Wolff","doi":"10.1089/jamp.2023.29092.rkw","DOIUrl":"10.1089/jamp.2023.29092.rkw","url":null,"abstract":"<p><p>Pharmacodynamics (PD) is discussed in relation to inhalation exposure to inhaled pharmaceutical and toxic agents. Clearly PD is closely related to pharmacokinetics, and this relation is illustrated with reference to inhaled insulin. PD can be related to pharmacologic responses, and some examples are cited. However, PD can also be thought of as the improvement or deterioration in lung disease state. Some of the major PD endpoints, including histopathology, pulmonary function, and bronchoalveolar lavage are reviewed. Brief reference is also given to other specialty biomarkers of PD response.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 5","pages":"275-280"},"PeriodicalIF":3.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49677697","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":"There Is a Risk of Spread During a Nebulization Session in a Patient with COVID-19.","authors":"Christophe Thibon,&nbsp;Laurent Vecellio,&nbsp;Leila Belkhir,&nbsp;Jean-Christophe Dubus,&nbsp;Annie Robert,&nbsp;Benoît Kabamba,&nbsp;Gregory Reychler","doi":"10.1089/jamp.2023.0010","DOIUrl":"10.1089/jamp.2023.0010","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> A hypothetical risk of SARS-CoV-2 airborne transmission through nebulization was suggested based on a potential environmental contamination by the fugitive aerosol emitted in the environment during the procedure. The aim of this study was to verify this risk from the fugitive aerosol emitted by COVID-19 patients during one nebulization session. <b><i>Methods:</i></b> In this cohort study, COVID-19 patients treated with nebulization were recruited at their admission to the hospital. Patients had to perform a nebulization session while a BioSampler^® and a pump were used to vacuum the fugitive aerosol and collect it for SARS-CoV-2 RNA detection. <b><i>Results:</i></b> Ten consecutive patients hospitalized with COVID-19 were recruited. The median viral load was 6.5 × 10⁶ copies/mL. Two out of the 10 samples from the fugitive aerosol collected were positive to SARS-CoV-2. <b><i>Conclusion:</i></b> The risk of fugitive aerosol contamination with SARS-CoV-2 during nebulization has now been verified.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"268-274"},"PeriodicalIF":3.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10433927","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":"The Pharmacokinetics of Inhaled Drugs.","authors":"Glyn Taylor","doi":"10.1089/jamp.2023.29091.gt","DOIUrl":"10.1089/jamp.2023.29091.gt","url":null,"abstract":"<p><p>The pharmacokinetic (PK) profile of a drug after inhalation may differ quite markedly from that seen after dosing by other routes of administration. Drugs may be administered to the lung to elicit a local action or as a portal for systemic delivery of the drug to its site of action elsewhere in the body. Some knowledge of PK is important for both locally- and systemically-acting drugs. For a systemically-acting drug, the plasma concentration-time profile shares some similarities with drug given by the oral or intravenous routes, since the plasma concentrations (after the distribution phase) will be in equilibrium with concentrations at the site of action. For a locally-acting drug, however, the plasma concentrations reflect its fate after it has been absorbed and removed from the airways, and not what is available to its site of action in the lung. Consequently, those typical PK parameters which are determined from plasma concentration measurements, e.g., area under the curve (AUC), C_max, t_max and post-peak t1/2 may provide information on the deposition and absorption of drugs from the lung; however, the information from these parameters becomes more complicated to decipher for those drugs which are locally-acting in the lung. Additionally, the plasma concentration profile for both locally- and systemically-acting drugs will not only reflect drug absorbed from the lung but also that absorbed from the gastrointestinal (GI) tract from the portion of the dose which is swallowed. This absorption from the GI tract adds a further complication to the interpretation of plasma concentrations, particularly for locally-acting drugs. The influence of physiological and pathological factors needs to be considered in the absorption of some inhaled drugs. The absorption of some hydrophilic drugs is influenced by the inspiratory maneuver used during initial inhalation of the drug, and at later times after deposition. Similarly, the effects of smoking have been shown to increase lung permeability and increase the absorption of certain hydrophilic drugs. The effects of different disease states of the lung have less defined influences on absorption into the systemic circulation.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 5","pages":"281-288"},"PeriodicalIF":3.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49677698","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":"Aerosol Delivery of a Novel Recombinant Modified Superoxide Dismutase Protein Reduces Oxidant Injury and Attenuates <i>Escherichia coli</i> Induced Lung Injury in Rats.","authors":"Sean D McCarthy,&nbsp;Maura A Tilbury,&nbsp;Claire H Masterson,&nbsp;Ronan MacLoughlin,&nbsp;Héctor E González,&nbsp;John G Laffey,&nbsp;J Gerard Wall,&nbsp;Daniel O'Toole","doi":"10.1089/jamp.2022.0069","DOIUrl":"10.1089/jamp.2022.0069","url":null,"abstract":"<p><p><b><i>Background:</i></b> Acute respiratory distress syndrome (ARDS) is a life-threatening respiratory failure syndrome with diverse etiologies characterized by increased permeability of alveolar-capillary membranes, pulmonary edema, and acute onset hypoxemia. During the ARDS acute phase, neutrophil infiltration into the alveolar space results in uncontrolled release of reactive oxygen species (ROS) and proteases, overwhelming antioxidant defenses and causing alveolar epithelial and lung endothelial injury. <b><i>Objectives:</i></b> To investigate the therapeutic potential of a novel recombinant human Cu-Zn-superoxide dismutase (SOD) fusion protein in protecting against ROS injury and for aerosolized SOD delivery to treat <i>Escherichia coli</i> induced ARDS. <b><i>Methods:</i></b> Fusion proteins incorporating human Cu-Zn-SOD (hSOD1), with (pep1-hSOD1-his) and without (hSOD1-his) a fused hyaluronic acid-binding peptide, were expressed in <i>E. coli</i>. Purified proteins were evaluated in <i>in vitro</i> assays with human bronchial epithelial cells and through aerosolized delivery to the lung of an <i>E. coli</i>-induced ARDS rat model. <b><i>Results:</i></b> SOD proteins exhibited high SOD activity <i>in vitro</i> and protected bronchial epithelial cells from oxidative damage. hSOD1-his and pep1-hSOD1-his retained SOD activity postnebulization and exhibited no adverse effects in the rat. Pep1-hSOD1-his administered through instillation or nebulization to the lung of an <i>E. coli</i>-induced pneumonia rat improved arterial oxygenation and lactate levels compared to vehicle after 48 hours. Static lung compliance was improved when the pep1-hSOD1-his protein was delivered by instillation. White cell infiltration to the lung was significantly reduced by aerosolized delivery of protein, and reduction of cytokine-induced neutrophil chemoattractant-1, interferon-gamma, and interleukin 6 pro-inflammatory cytokine concentrations in bronchoalveolar lavage was observed. <b><i>Conclusions:</i></b> Aerosol delivery of a novel recombinant modified SOD protein reduces oxidant injury and attenuates <i>E. coli</i> induced lung injury in rats. The results provide a strong basis for further investigation of the therapeutic potential of hSOD1 in the treatment of ARDS.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"246-256"},"PeriodicalIF":3.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10084999","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":"Aerosol Particle Size Influences the Infectious Dose and Disease Severity in a Golden Syrian Hamster Model of Inhalational COVID-19.","authors":"Jeremy A Boydston, Jennifer Biryukov, John J Yeager, Heather A Zimmerman, Gregory Williams, Brian Green, Amy L Reese, Katie Beck, Jordan K Bohannon, David Miller, Denise Freeburger, Amanda Graham, Victoria Wahl, Michael C Hevey, Paul A Dabisch","doi":"10.1089/jamp.2022.0072","DOIUrl":"10.1089/jamp.2022.0072","url":null,"abstract":"<p><p><b><i>Background:</i></b> Significant evidence suggests that SARS-CoV-2 can be transmitted via respiratory aerosols, which are known to vary as a function of respiratory activity. Most animal models examine disease presentation following inhalation of small-particle aerosols similar to those generated during quiet breathing or speaking. However, despite evidence that particle size can influence dose-infectivity relationships and disease presentation for other microorganisms, no studies have examined the infectivity of SARS-CoV-2 contained in larger particle aerosols similar to those produced during coughing, singing, or talking. Therefore, the aim of the present study was to assess the influence of aerodynamic diameter on the infectivity and virulence of aerosols containing SARS-CoV-2 in a hamster model of inhalational COVID-19. <b><i>Methods:</i></b> Dose-response relationships were assessed for two different aerosol particle size distributions, with mass median aerodynamic diameters (MMADs) of 1.3 and 5.2 μm in groups of Syrian hamsters exposed to aerosols containing SARS-CoV-2. <b><i>Results:</i></b> Disease was characterized by viral shedding in oropharyngeal swabs, increased respiratory rate, decreased activity, and decreased weight gain. Aerosol particle size significantly influenced the median doses to induce seroconversion and viral shedding, with both increasing ∼30-fold when the MMAD was increased. In addition, disease presentation was dose-dependent, with seroconversion and viral shedding occurring at lower doses than symptomatic disease characterized by increased respiratory rate and decreased activity. <b><i>Conclusions:</i></b> These results suggest that aerosol particle size may be an important factor influencing the risk of COVID-19 transmission and needs to be considered when developing animal models of disease. This result agrees with numerous previous studies with other microorganisms and animal species, suggesting that it would be generally translatable across different species. However, it should be noted that the absolute magnitude of the observed shifts in the median doses obtained with the specific particle sizes utilized herein may not be directly applicable to other species.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"235-245"},"PeriodicalIF":2.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10192713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}