Journal of Aerosol Medicine and Pulmonary Drug Delivery最新文献

{"title":"Stability and Activity of Interferon Beta to Treat Idiopathic Pulmonary Fibrosis with Different Nebulizer Technologies.","authors":"Edgar Hernan Cuevas Brun,&nbsp;Zuo-Yi Hong,&nbsp;Yuan-Ming Hsu,&nbsp;Ciou-Ting Wang,&nbsp;Dai-Jung Chung,&nbsp;Shang-Kok Ng,&nbsp;Yau-Hsuan Lee,&nbsp;Tzu-Tang Wei","doi":"10.1089/jamp.2022.0020","DOIUrl":"https://doi.org/10.1089/jamp.2022.0020","url":null,"abstract":"<p><p><b><i>Background:</i></b> Idiopathic pulmonary fibrosis (IPF) is a serious lung disease characterized by lung scarring, which results in breathing difficulty. Currently, patients with IPF exhibit a poor survival rate and have access to very limited therapeutic options. Interferon beta (IFN-β) has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of relapsing forms of multiple sclerosis, and it has also been shown to exhibit therapeutic potential in IPF. However, clinical use of IFN-β did not lead to improved overall survival in IPF patients in existing studies. One possibility is the limited efficiency of IFN-β delivery through intravenous or subcutaneous injection. <b><i>Materials and Methods:</i></b> The aerosol particle size distribution was determined with a laser diffraction particle size analyzer to characterize the droplet size and fine particle fraction generated by three types of nebulizers: jet, ultrasonic, and mesh. A breathing simulator was used to assess the delivery efficiency of IFN-β, and the temperature in the medication reservoirs was monitored with a thermocouple during nebulization. To further evaluate the antifibrotic activity of IFN-β pre- and postnebulization, bleomycin (BLM)- or transforming growth factor-beta (TGF-β)-treated human lung fibroblast (HLF) cells were used. Cell viability was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Transwell migration assay and Q-PCR analysis were used to evaluate cell migration and the myofibroblast differentiation ability, respectively. IFN-β protein samples were prepared using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) sample loading buffer, and the expression of IFN-β was assessed by western blotting. <b><i>Results:</i></b> Among the current drug delivery systems, aerosolized medication has shown increased efficacy of drug delivery for treating respiratory diseases when compared with parenteral drugs. It was found that neither the structural integrity nor the biological function of nebulized IFN-β was compromised by the nebulization process of the mesh nebulizer. In addition, in BLM dose-response or TGF-β-induced lung fibroblast proliferation assays, these effects could be reversed by both parenteral and inhaled IFN-β nebulized with the mesh nebulizer. Nebulized IFN-β with the mesh nebulizer also significantly inhibited the migration and myofibroblast differentiation ability of TGF-β-treated HLF cells. <b><i>Conclusions:</i></b> The investigations revealed the potential efficacy of IFN-β in the treatment of IPF with the mesh nebulizer, demonstrating the higher efficiency of IFN-β delivered through the mesh nebulizer.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 2","pages":"55-64"},"PeriodicalIF":3.4,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9471839","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":"Resveratrol-Loaded Dipalmitoylphosphatidylcholine Liposomal Large Porous Microparticle Inhalations for the Treatment of Bacterial Pneumonia Caused by <i>Acinetobacter baumannii</i>.","authors":"Zicheng Yu,&nbsp;Tingting Wu,&nbsp;Xiaoyan Liu,&nbsp;Hongjun Chen,&nbsp;Chunxia Ren,&nbsp;Lifei Zhu","doi":"10.1089/jamp.2021.0049","DOIUrl":"https://doi.org/10.1089/jamp.2021.0049","url":null,"abstract":"<p><p><b><i>Background:</i></b> <i>Acinetobacter baumannii</i>-mediated bacterial pneumonia is a common disease that is harmful to human health. Dipalmitoylphosphatidylcholine (DPPC) is the major lipid component of the pulmonary surfactant (PS) found in the alveolar space; the PS helps to keep surface tension low, which allows for improved oxygen delivery. Resveratrol (RE) is a phytoalexin found in plants that is released in response to injury or infection. The therapeutic effect of Re is limited due to its low solubility and bioavailability. In this study, we report pulmonary delivery of Re-loaded DPPC liposomal large porous microparticles (RDLPMs) for treatment of <i>A. baumannii</i>-induced pneumonia. <b><i>Methods:</i></b> Novel RDLPMs were prepared by rotary evaporation and a freeze-drying method in this study. RDLPMs were evaluated by the particle size, electric potential, <i>in vitro</i> release, and particle size distribution. A rat model of <i>A. baumannii</i>-mediated pneumonia was established and used for pharmacodynamic evaluations. <b><i>Results:</i></b> The Re-loaded DPPC liposomes (RDLs) consisted of Re/DPPC (1:3, mol/mol) and DPPC/cholesterol (3:1, w/w), with a hydration time of 15 minutes. The RDLs had a high encapsulation efficiency of 69.8% ± 1.6%, a mean size of 191.5 ± 4.5 nm, and a high zeta potential of 12.4 ± 1.5 mV. The RDLPMs were composed of mannitol/large porous microparticles/RDLs (1:4:2, w/w/w) and had a loading efficiency of 2.20% ± 0.24%. The RDLPMs had an aerodynamic diameter (2.73 ± 0.65 μm), a good fluidity (28.30° ± 6.13°), and demonstrated high lung deposition (fine particle fraction = 43.33%). Surprisingly, while penicillin showed better microbial inhibition than the RDLPMs and Re groups <i>in vitro</i>, the RDLPMs were more effective <i>in vivo</i>. <b><i>Conclusion:</i></b> The RDLPMs showed good powder properties for pulmonary delivery. The RDLPMs may inhibit the nuclear factor kappa-B pathway and downregulate the expression of cytokines downstream of tumor necrosis factor-α and interleukin-1β. As well as, RDLPMs demonstrated some antibacterial properties against <i>A. baumannii</i> bacteria. Re, when delivered in RDLPMs as a dry powder inhaler, is a promising substitute for antibiotics in the treatment of <i>A. baumannii</i> pneumonia.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 1","pages":"2-11"},"PeriodicalIF":3.4,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9576166","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":"Positron Emission Tomography-Computed Tomography Imaging of Selective Lobar Delivery of Stem Cells in <i>Ex Vivo</i> Lung Model of Mechanical Ventilation.","authors":"Luiz Maracaja,&nbsp;Ashish K Khanna,&nbsp;Sean V Murphy,&nbsp;Danielle L V Maracaja,&nbsp;Magan R Lane,&nbsp;Oula Khoury,&nbsp;Josh Tan,&nbsp;Naresh Damuka,&nbsp;Freda F Crawford,&nbsp;Joseph A Bottoms,&nbsp;Mack D Miller,&nbsp;David W Kaczka,&nbsp;James Eric Jordam,&nbsp;Kiran Kumar Solingapuram Sai","doi":"10.1089/jamp.2022.0013","DOIUrl":"https://doi.org/10.1089/jamp.2022.0013","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> The delivery of cell therapies may be an important frontier to treat different respiratory diseases in the near future. However, the cell size, delivery conditions, cell viability, and effect in the pulmonary function are critical factors. We performed a proof-of-concept experiment using <i>ex vivo</i> lungs and novel subglottic airway device that allows for selective lobar isolation and administration of drugs and biologics in liquid solution deep into the lung tissues, while simultaneously ventilating the rest of the lung lobes. <b><i>Methods:</i></b> We used radiolabeled cells and positron emission tomography-computed tomography (PET-CT) imaging to demonstrate the feasibility of high-yield cell delivery to a specifically targeted lobe. This study proposes an alternative delivery method of live cells labeled with radioactive isotope into the lung parenchyma and tracks the cell delivery using PET-CT imaging. The technique combines selective lobar isolation and lobar infusion to carry large particles distal to the trachea, subtending bronchial segments and reaching alveoli in targeted regions. <b><i>Results:</i></b> The solution with cells and carrier achieved a complete and homogeneous lobar distribution. An increase in tissue density was shown on the computed tomography (CT) scan, and the PET-CT imaging demonstrated retention of the activity at central, peripheral lung parenchyma, and pleural surface. The increase in CT density and metabolic activity of the isotope was restricted to the desired lobe only without leak to other lobes. <b><i>Conclusion:</i></b> The selective lobe delivery is targeted and imaging-guided by bronchoscopy and CT to a specific diseased lobe during mechanical ventilation. The feasibility of high-yield cell delivery demonstrated in this study will lead to the development of potential novel therapies that contribute to lung health.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 1","pages":"20-26"},"PeriodicalIF":3.4,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9942179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9591837","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}

{"title":"<i>In Vitro</i> Drug Delivery of a Fixed-Dose Combination of Fluticasone Furoate/Umeclidinium/Vilanterol from a Dry Powder Inhaler.","authors":"Melanie Hamilton,&nbsp;Martin Anderson,&nbsp;Rajiv Dhand,&nbsp;Oonagh Patmore,&nbsp;David Prime,&nbsp;Edward Taylor","doi":"10.1089/jamp.2021.0061","DOIUrl":"https://doi.org/10.1089/jamp.2021.0061","url":null,"abstract":"<p><p><b><i>Background:</i></b> Dry powder inhalers (DPIs) require patients to impart sufficient energy through inhalation to ensure adequate dose emission, medication deaggregation, and resultant particle sizes suitable for lung deposition. There is an ongoing debate regarding the level of inspiratory effort, and therefore inspiratory flow rate, needed for optimal dose delivery from DPIs. <b><i>Materials and Methods:</i></b> The delivered dose (DD) and fine particle fraction (FPF) for each component of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 μg and FF/UMEC/VI 200/62.5/25 μg ELLIPTA DPIs were assessed at flow rates of 30, 60, and 90 L/min. Electronic lung (eLung) (eLung; an electronic breathing simulator) assessments were conducted to replicate inhalation profiles representing a wide range of inhalation parameters and inhaled volumes achieved by patients with chronic obstructive pulmonary disease (COPD) or asthma of all severity levels. Timing and duration of dose emission were assessed using a particle detector located at the entrance of an anatomical throat cast attached to the eLung. <b><i>Results:</i></b> During DD assessment, a mean of >80% of the nominal blister content (nbc) was emitted from the ELLIPTA DPI at all flow rates. In Next Generation Impactor assessments, the observed mean DD across flow rates for FF/UMEC/VI 100/62.5/25 μg ranged from 85.9% to 97.0% of nbc and 84.0% to 93.5% for FF/UMEC/VI 200/62.5/25 μg. In eLung assessments, 82.8% to 95.5% of nbc was delivered across the PIF range, 43.5 to 129.9 L/min (COPD), and 85.1% to 92.3% across the PIF range, 67.4 to 129.9 L/min (asthma). The FPF (mass <5 μm; % nbc) for each component was comparable across all flow rates and inhalation profiles. Dose emission timings indicated that near-complete dose emission occurs before reaching PIF. <b><i>Conclusions:</i></b> Dose delivery assessments across all flow rates and inhalation profiles indicate that patients with all severity levels of COPD or asthma can achieve the required inspiratory effort for efficient delivery of all components of FF/UMEC/VI from the ELLIPTA DPI. Dose emission profiles suggest rapid and near-complete dose delivery from the ELLIPTA DPI before reaching PIF.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 1","pages":"34-43"},"PeriodicalIF":3.4,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9942181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9576167","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}

{"title":"The Use of Single Photon Emission Computed Tomography in Aerosol Medicine.","authors":"John S Fleming","doi":"10.1089/jamp.2023.29077.jsf","DOIUrl":"https://doi.org/10.1089/jamp.2023.29077.jsf","url":null,"abstract":"<p><p>Imaging of radiolabeled aerosols provides useful <i>in vivo</i> data on both the initial site of deposition and its subsequent transport by mucociliary clearance and epithelial permeability. Single Photon Emission Computed Tomography (SPECT) uses a gamma camera with multiple rotating heads to produce three-dimensional (3D) images of inhaled radioaerosol labeled with technetium-99m. This enables total lung deposition and its 3D regional distribution to be quantified. Aligned 3D images of lung structure allow deposition data to be related to lung anatomy. Mucociliary clearance or epithelial permeability can be assessed from a time series of SPECT aerosol images. SPECT is slightly superior to planar imaging for measuring total lung deposition. However, it is more complex to use, and for studies where total lung deposition is the endpoint, planar imaging is recommended. However, SPECT has been shown to be clearly superior to planar imaging for assessing regional distribution of aerosol and is the method of choice for this purpose. It therefore has applications in studying the influence of regional deposition on clinical effectiveness and also in validating computer models of deposition. The inability to directly radiolabel drug molecules with ^99mTc is a clear disadvantage of SPECT and limits its potential use for pharmacokinetic studies. SPECT provides a wealth of data on aerosol deposition, which has been relatively underused at present. Optimal methods of analyzing and interpreting the data need to be developed. SPECT can also, in principle, provide detailed information of mucociliary clearance and has the potential to significantly improve knowledge of this process and hence clarify the role of clearance as a biomarker.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 1","pages":"44-53"},"PeriodicalIF":3.4,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9591838","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":"An Investigation into the Factors Associated with Incorrect Use of a Pressurized Metered-Dose Inhaler in Japanese Patients.","authors":"Hiroshi Ohnishi,&nbsp;Masafumi Okazaki,&nbsp;Kazuki Anabuki,&nbsp;Shin Akita,&nbsp;Shigeo Kawase,&nbsp;Kimiko Sakai Tsuji,&nbsp;Mitsuhiko Miyamura,&nbsp;Akihito Yokoyama","doi":"10.1089/jamp.2022.0018","DOIUrl":"https://doi.org/10.1089/jamp.2022.0018","url":null,"abstract":"<p><p><b><i>Rationale:</i></b> Inhalation of the correct dose of a short-acting beta 2 agonist (SABA) from a pressurized metered-dose inhaler (pMDI) is essential for the relief of symptoms in patients with asthma and/or chronic obstructive pulmonary disease. The aim of this study was to evaluate the prevalence and factors associated with the incorrect use of a pMDI. <b><i>Methods:</i></b> This study retrospectively assessed the electronic medical records of 161 patients with various respiratory diseases. The patients had never used a pMDI and underwent training by pharmacists educated in the use of a pMDI followed by bronchodilator reversibility testing at our hospital. The patients' characteristics and various lung capacity parameters were evaluated for association with the incorrect use of a pMDI. <b><i>Results:</i></b> Thirty-nine of the 161 (24.2%) patients, including 46% of 28 patients older than 80 years, used the pMDI incorrectly, mainly because of incoordination between activation of the device and inhalation (<i>n</i> = 11), inadequate strength to manipulate the device (<i>n</i> = 9), too short duration of inhalation (<i>n</i> = 6), and difficulty in breath holding (<i>n</i> = 3). Advanced age; lower height; and decreased lung volumes, including vital capacity (VC), inspiratory capacity, inspiratory reserve volume (IRV), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow rate, were associated with the incorrect use of a pMDI. Neither the body weight, tidal volume, expiratory reserve volume, %FVC predicted, %FEV1 predicted, nor FEV1% was associated with the incorrect use of a pMDI. Multivariate binomial logistic regression analysis identified decreased IRV as the only independent predictor associated with the incorrect use of a pMDI. <b><i>Conclusions:</i></b> Physicians should be aware that elderly patients or patients with decreased IRV might be unable to obtain the correct SABA dose from a pMDI. A large-scale prospective study is required to confirm these findings from our retrospective study with a small group of patients.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 1","pages":"12-19"},"PeriodicalIF":3.4,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9215892","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":"Application of Machine Learning for Segmentation of the Pulmonary Acinus Imaged by Synchrotron X-Ray Tomography.","authors":"Branko Arsic,&nbsp;Igor Saveljic,&nbsp;Frank S Henry,&nbsp;Nenad Filipovic,&nbsp;Akira Tsuda","doi":"10.1089/jamp.2022.0051","DOIUrl":"https://doi.org/10.1089/jamp.2022.0051","url":null,"abstract":"<p><p><b><i>Background:</i></b> To assess the effectiveness of inhalation therapy, it is important to evaluate the lungs' structure; thus, visualization of the entire lungs at the level of the alveoli is necessary. To achieve this goal, the applied visualization technique must satisfy the following two conditions simultaneously: (1) it has to obtain images of the entire lungs, since one part of the lungs is influenced by the other parts, and (2) the images have to capture the detailed structure of the alveolus/acinus in which gas exchange occurs. However, current visualization techniques do not fulfill these two conditions simultaneously. Segmentation is a process in which each pixel of the obtained high-resolution images is simplified (i.e., the representation of an image is changed by categorizing and modifying each pixel) so that we can perform three-dimensional volume rendering. One of the bottlenecks of current approaches is that the accuracy of the segmentation of each image has to be evaluated on the outcome of the process (mainly by an expert). It is a formidable task to evaluate the astronomically large numbers of images that would be required to resolve the entire lungs in high resolution. <b><i>Methods:</i></b> To overcome this challenge, we propose a new approach based on machine learning (ML) techniques for the validation step. <b><i>Results:</i></b> We demonstrate the accuracy of the segmentation process itself by comparison with previously validated images. In this ML approach, to achieve a reasonable accuracy, millions/billions of parameters used for segmentation have to be optimized. This computationally demanding new approach is achievable only due to recent dramatic increases in computation power. <b><i>Conclusion:</i></b> The objective of this article is to explain the advantages of ML over the classical approach for acinar imaging.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 1","pages":"27-33"},"PeriodicalIF":3.4,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a4/06/jamp.2022.0051.PMC9942171.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9222232","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}

{"title":"Acknowledgment of Reviewers 2022.","authors":"","doi":"10.1089/jamp.2023.29083.ack","DOIUrl":"https://doi.org/10.1089/jamp.2023.29083.ack","url":null,"abstract":"","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10485612","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":"Preclinical Studies of the Nebulized Delivery of Liposomal Amphotericin B.","authors":"Sagar Kothari,&nbsp;Steven G Kefalos,&nbsp;Nicholas D Hages,&nbsp;Timothy E Corcoran,&nbsp;Shahid Husain","doi":"10.1089/jamp.2022.0003","DOIUrl":"https://doi.org/10.1089/jamp.2022.0003","url":null,"abstract":"<p><p><b><i>Background:</i></b> Intravenous liposomal amphotericin B (L-AMB) has accompanying side effects that may be diminished when administering an inhaled form. Delivery systems for inhaled or aerosolized L-AMB vary, and there has not been a recent comparison of available systems to date. <b><i>Methods:</i></b> We compared three differently designed nebulizer delivery systems for the inhaled delivery of L-AMB to determine the best combination of efficient lung dosing and treatment time. Aerosol size was measured using a Malvern Mastersizer, and five separate nebulizers were tested. For drug output measurements, a Harvard Lung was used, and aerosol was collected using HEPA filters. <b><i>Results:</i></b> Overall aerosol size characteristics were similar for all devices with volume median diameters in the 4-5 μm range. The highest inhaled dose was delivered by the AeroEclipse. The Aerogen and the AeroEclipse had similar predicted pulmonary doses, and the AeroEclipse had the highest pulmonary delivery rates. <b><i>Conclusion:</i></b> The AeroEclipse nebulizer may provide more efficient delivery in a shorter amount of time; however, human studies are warranted to assess the safety, tolerability, and efficacy of inhaled delivery of L-AMB from this system.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"35 6","pages":"307-312"},"PeriodicalIF":3.4,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10830379","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":"Comparison of Dose-Response Relationships for Two Isolates of SARS-CoV-2 in a Nonhuman Primate Model of Inhalational COVID-19.","authors":"Paul A Dabisch, Jaleal S Sanjak, Jeremy A Boydston, John Yeager, Artemas Herzog, Jennifer Biryukov, Katie Beck, Danh Do, Brittany G Seman, Brian Green, Jordan K Bohannon, Brian Holland, David Miller, Taylor Ammons, Denise Freeburger, Susan Miller, Tammy Jenkins, Sherry Rippeon, James Miller, David Clarke, Emmanuel Manan, Ashley Patty, Kim Rhodes, Tina Sweeney, Michael Winpigler, Louis A Altamura, Heather Zimmerman, Alec S Hail, Victoria Wahl, Michael Hevey","doi":"10.1089/jamp.2022.0043","DOIUrl":"10.1089/jamp.2022.0043","url":null,"abstract":"<p><p><b><i>Background:</i></b> As the COVID-19 pandemic has progressed, numerous variants of SARS-CoV-2 have arisen, with several displaying increased transmissibility. <b><i>Methods:</i></b> The present study compared dose-response relationships and disease presentation in nonhuman primates infected with aerosols containing an isolate of the Gamma variant of SARS-CoV-2 to the results of our previous study with the earlier WA-1 isolate of SARS-CoV-2. <b><i>Results:</i></b> Disease in Gamma-infected animals was mild, characterized by dose-dependent fever and oronasal shedding of virus. Differences were observed in shedding in the upper respiratory tract between Gamma- and WA-1-infected animals that have the potential to influence disease transmission. Specifically, the estimated median doses for shedding of viral RNA or infectious virus in nasal swabs were approximately 10-fold lower for the Gamma variant than the WA-1 isolate. Given that the median doses for fever were similar, this suggests that there is a greater difference between the median doses for viral shedding and fever for Gamma than for WA-1 and potentially an increased range of doses for Gamma over which asymptomatic shedding and disease transmission are possible. <b><i>Conclusions:</i></b> These results complement those of previous studies, which suggested that differences in exposure dose may help to explain the range of clinical disease presentations observed in individuals with COVID-19, highlighting the importance of public health measures designed to limit exposure dose, such as masking and social distancing. The dose-response data provided by this study are important to inform disease transmission and hazard modeling, as well as to inform dose selection in future studies examining the efficacy of therapeutics and vaccines in animal models of inhalational COVID-19.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"35 6","pages":"296-306"},"PeriodicalIF":2.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c5/39/jamp.2022.0043.PMC9807281.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10517637","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}