Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine最新文献_第4页

Preclinical safety evaluation of inhaled cyclosporine in propylene glycol. 丙二醇中吸入环孢素的临床前安全性评价。

Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine Pub Date : 2007-01-01 DOI: 10.1089/jam.2007.0626

Tao Wang, Sarah Noonberg, Ronald Steigerwalt, Maryellen Lynch, Rosemary A Kovelesky, Carlos A Rodríguez, Katherine Sprugel, Nancy Turner

{"title":"Preclinical safety evaluation of inhaled cyclosporine in propylene glycol.","authors":"Tao Wang, Sarah Noonberg, Ronald Steigerwalt, Maryellen Lynch, Rosemary A Kovelesky, Carlos A Rodríguez, Katherine Sprugel, Nancy Turner","doi":"10.1089/jam.2007.0626","DOIUrl":"https://doi.org/10.1089/jam.2007.0626","url":null,"abstract":"Cyclosporine inhalation solution has the potential to improve outcomes following lung transplantation by delivering high concentrations of an immunosuppressant directly to the allograft while minimizing systemic drug exposure and associated toxicity. The objective of these studies was to evaluate the potential toxicity of aerosolized cyclosporine formulated in propylene glycol when given by inhalation route to rats and dogs for 28 days. Sprague-Dawley rats received total inhaled doses of 0 (air), 0 (vehicle, propylene glycol), 7.4, 24.3, and 53.9 mg cyclosporine/kg/day. In a separate study, beagle dogs were exposed to 0, 4.4, 7.7, and 9.7 mg cyclosporine/kg/day. Endpoints used to evaluate potential toxicity of inhaled cyclosporine were clinical observations, body weight, food consumption, respiratory functions, toxicokinetics, and clinical/anatomic pathology. Daily administration of aerosolized cyclosporine did not result in observable accumulation of cyclosporine in blood or lung tissue. Toxicokinetic analysis from the rat study showed that the exposure of cyclosporine was approximately 18 times higher in the lung tissue compared to the blood. Systemic effects were consistent with those known for cyclosporine. There was no unexpected systemic toxicity or clinically limiting local respiratory toxicity associated with inhalation exposure to cyclosporine inhalation solution at exposures up to 2.7 times the maximum human exposure in either rats or dogs. There were no respiratory or systemic effects of high doses of propylene glycol relative to air controls. These preclinical studies demonstrate the safety of aerosolized cyclosporine in propylene glycol and support its continued clinical investigation in patients undergoing allogeneic lung transplantation.","PeriodicalId":14878,"journal":{"name":"Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine","volume":"20 4","pages":"417-28"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jam.2007.0626","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27191205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 25

The interface between the device and the patient: masks, mouthpieces, and "others." Introduction. 设备和病人之间的接口:口罩、嘴和“其他”。介绍。

Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine Pub Date : 2007-01-01 DOI: 10.1089/jam.2006.0003

Joseph L Rau, Gerald C Smaldone

引用次数: 2

Jet nebulizers versus pressurized metered dose inhalers with valved holding chambers: effects of the facemask on aerosol delivery. 喷射喷雾器与带阀保持室的加压计量吸入器:面罩对气溶胶输送的影响。

Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine Pub Date : 2007-01-01 DOI: 10.1089/jam.2007.0588

Kurt Nikander, Elna Berg, Gerald C Smaldone

{"title":"Jet nebulizers versus pressurized metered dose inhalers with valved holding chambers: effects of the facemask on aerosol delivery.","authors":"Kurt Nikander, Elna Berg, Gerald C Smaldone","doi":"10.1089/jam.2007.0588","DOIUrl":"https://doi.org/10.1089/jam.2007.0588","url":null,"abstract":"The delivery of an aerosolized drug to a child is a complex process requiring an interaction between parent, child, and inhalation device. Recent studies have shown that the facemask can be a key factor affecting aerosol delivery, particularly the influence of leaks between the facemask and the face. To further quantify these effects and design around them, we have developed a bench model consisting of a breathing simulator, an inhaled mass filter, and a \"pediatric face.\" This paper reviews the development of this model and details important decisions made in its configuration, particularly inhaled mass filter location (e.g., between device and facemask, or in mouth) and mouth diameter (4 or 18 mm). With the final design, we used the model to measure the impact of the \"blow-by\" technique on nebulizer inhaled mass. In a separate series of experiments, we studied the effects of a \"crying\" pediatric breathing pattern on inhaled mass for both nebulizers and pressurized metered dose inhalers with valved holding chambers (pMDI VHCs). Results indicated that the location of the inhaled mass filter was a critical factor in assessing aerosol delivery through facemasks and that the \"mouth diameter\" was not an important variable. Failure to locate the filter in the mouth behind the face, especially for jet nebulizers, failed to accurately measure effects of the facemask and significantly overestimated aerosol delivery. Blow-by results indicated that a 1-cm gap between the facemask and the face was not critical when using a front-loaded facemask. Finally, even with optimal design, the combination of an aerosol generator and facemask with a crying breathing pattern reduced the inhaled mass to 1% of the label dose.","PeriodicalId":14878,"journal":{"name":"Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine","volume":"20 Suppl 1 ","pages":"S46-55; discussion S55-8"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jam.2007.0588","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26645666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 50

Devices for aerosol delivery to treat sinusitis. 用于治疗鼻窦炎的喷雾输送装置。

Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine Pub Date : 2007-01-01 DOI: 10.1089/jam.2007.0569

Beth L Laube

{"title":"Devices for aerosol delivery to treat sinusitis.","authors":"Beth L Laube","doi":"10.1089/jam.2007.0569","DOIUrl":"https://doi.org/10.1089/jam.2007.0569","url":null,"abstract":"Compared to research into aerosolized delivery of drugs to treat lung disease, research into nasal delivery of aerosolized drugs to treat sinusitis has been significantly neglected. This is despite the fact that more individuals suffer from sinusitis in the United States than suffer from asthma, and its consequences lead to considerable amounts of discomfort, lost work days, and money spent on health care. A number of studies have shown that a high proportion of aerosolized medications delivered by metered dose inhalers (MDIs) and aqueous spray devices deposits in the anterior one-third of the nasal cavity. However, the important targets for treating sinusitis lie beyond this region. These include the middle meatus, the superior and posterior regions of the nasal cavity and the sinuses themselves. This review examines the particle-related and device-related factors that are known to improve intranasal delivery of aerosolized medications to these targets and their efficacy in patients with disease. Based on this review, it is recommended that companies that are interested in improving aerosol delivery to treat sinusitis utilize both in vivo imaging modalities and in vitro models of the nasal cavity and sinuses to assess intranasal aerosol delivery and device performance during the development stage. Once device design has been optimized, it is recommended that device manufacturers and pharmaceutical companies move beyond the current reliance on anecdotal reporting and uncontrolled studies to clinical trials that are randomized and placebo-controlled and that quantify changes both in symptoms and in functional parameters to determine drug efficacy with their device.","PeriodicalId":14878,"journal":{"name":"Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine","volume":"20 Suppl 1 ","pages":"S5-17; discussion S17-8"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jam.2007.0569","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26645667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 71

Studies of the human oropharyngeal airspaces using magnetic resonance imaging IV--the oropharyngeal retention effect for four inhalation delivery systems. 人体口咽部空气空间的磁共振成像研究——四种吸入输送系统的口咽部滞留效应

Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine Pub Date : 2007-01-01 DOI: 10.1089/jam.2007.0566

Patricia K P Burnell, Lars Asking, Lars Borgström, Steve C Nichols, Bo Olsson, David Prime, Ian Shrubb

{"title":"Studies of the human oropharyngeal airspaces using magnetic resonance imaging IV--the oropharyngeal retention effect for four inhalation delivery systems.","authors":"Patricia K P Burnell, Lars Asking, Lars Borgström, Steve C Nichols, Bo Olsson, David Prime, Ian Shrubb","doi":"10.1089/jam.2007.0566","DOIUrl":"https://doi.org/10.1089/jam.2007.0566","url":null,"abstract":"Magnetic resonance imaging (MRI) of the oropharyngeal region from 20 adult volunteers using four model inhalation devices (varying mouthpiece diameters, airflow resistances) and tidal breathing was carried out. Statistical analysis (convex hull method) selected 12 scans from 80 data sets representing the extremes of all dimensions in the population. Twelve physical mouth-throat models were made by stereolithography using the exact scan data. The aim was to produce models with varying dimensions to span the adult population, and to investigate if oropharyngeal dimensions affected throat retention for different delivery systems. In an in vitro analysis, the models were used to determine the retention effect of the oropharyngeal airspaces when drug aerosols were administered from four inhalation delivery systems: a pressurised metered dose inhaler (pMDI), two different dry powder inhalers (DPIs A and B), and a nebulizer. The aims of this work were to determine the key parameters governing mouth-throat retention and whether retention was dependent on the delivery system used. Characterizing the throat models by measuring 51 different dimensional variables enabled determination of the most influential variables for dose retention for each inhalation delivery system. Throat model retention was found to be dependent on the delivery system (pMDI approximately DPI(A) > DPI(B) > Neb.). The most influential variable was the total throat model volume. Throat models representing high, median, and low oropharyngeal filtration in healthy adults have been identified.","PeriodicalId":14878,"journal":{"name":"Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine","volume":"20 3","pages":"269-81"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jam.2007.0566","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40993046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 57

Relationship between airway reactivity induced by methacholine or ultrasonically nebulized distilled cold water and BAL fluid cellular constituents in patients with sulfur mustard gas-induced asthma. 甲胆碱与超声雾化蒸馏水对硫芥子气哮喘患者气道反应性及BAL液细胞成分的影响。

Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine Pub Date : 2007-01-01 DOI: 10.1089/jam.2007.0589

Ali Emad, Yasaman Emad

{"title":"Relationship between airway reactivity induced by methacholine or ultrasonically nebulized distilled cold water and BAL fluid cellular constituents in patients with sulfur mustard gas-induced asthma.","authors":"Ali Emad, Yasaman Emad","doi":"10.1089/jam.2007.0589","DOIUrl":"https://doi.org/10.1089/jam.2007.0589","url":null,"abstract":"The objective of this article was to evaluate the relationship between the bronchial reactivity to methacholine and distilled cold water and inflammatory bronchial alveolar lavage (BAL) cells in mustard gas-induced asthma. This was a randomized, crossover clinical study set in a university hospital. The patients were 17 veterans with mustard gas-induced asthma and 17 normal veterans as a control group. Inhalation challenges with ultrasonically nebulized distilled water and methacholine and BAL via bronchoscopy and were performed in all patients and subjects. All patients did sustain a 20% fall in FEV(1) after methacholine, whereas two of them did not with distilled cold water. The patients were sensitive to distilled cold water with a median PD20 of 8.44 +/- 6.55 mL and sensitive to methacholine with the median PC20 of 4.88 +/- 4.22 mg/mL. Significant correlation was found between PC20 of methacholine and PD20 of distilled cold water (r = -0.74, p = 0.005). The proportion of BAL macrophages was significantly lower in patients with asthma than in the control group (p = 0.001). The proportions of lymphocytes and neutrophils were similar in the two groups. The percentage of eosinophils was higher in BAL fluid from the asthmatics compared with that in BAL fluid from the control group (p < 0.001). The percentage of the BAL eosinophils significantly correlated with both PC20 of methacholine (r = - 0.58, p = 0.01) and PD20 of distilled cold water (r = -0.81, p = 0.002). No relationship between PC20 of methacholine or PD20 of distilled cold water was found for other inflammatory BAL cells. This study showed that in patients with mustard gas-induced asthma, the degree of airway responsiveness to both methacholine and distilled water was associated with the percentage of BAL eosinophils.","PeriodicalId":14878,"journal":{"name":"Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine","volume":"20 3","pages":"342-51"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jam.2007.0589","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40994705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

A simple mechanistic model of deposition of water-soluble aerosol particles in the mouth and throat. 水溶性气溶胶颗粒在口腔和喉部沉积的简单机理模型。

Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine Pub Date : 2007-01-01 DOI: 10.1089/jam.2007.0625

Christina Mitsakou, Dimitris Mitrakos, Panagiotis Neofytou, Christos Housiadas

{"title":"A simple mechanistic model of deposition of water-soluble aerosol particles in the mouth and throat.","authors":"Christina Mitsakou, Dimitris Mitrakos, Panagiotis Neofytou, Christos Housiadas","doi":"10.1089/jam.2007.0625","DOIUrl":"https://doi.org/10.1089/jam.2007.0625","url":null,"abstract":"Aerosol drugs are usually delivered to the lung by inhalation via the oral route, since aerosol deposition is much lower in the oral than in nasal airways. In the present study a practical, non-CFD-based, mechanistic model is developed, which permits an efficient calculation of deposition along the oral route with simple computational means. A simplified geometrical description of the mouth and throat region is used, based on a sequence of conducting ducts. The numerical model takes into account aerosol dynamics, which enables to express the impact on aerosol transport and deposition of the hygroscopic growth of water-soluble particles. Simulations are made for coarse particles in the range 1-17 microm, and the model predictions are found in good agreement with the available experimental data. The model predicts inertial impaction to be the dominant mechanism, and correctly reproduces the increase in the deposition with an increasing flow rate and particle diameter. Higher deposition is calculated in the oropharyngeal region than the laryngeal region, due to the significant flow direction change and constriction at the end of the oral cavity. According to the model, highly soluble particles may deposit up to 50% more than inert aerosols in the mouth-throat region. The proposed model will be useful for quick, practical calculations of deposition with a full account of aerosol dynamical processes.","PeriodicalId":14878,"journal":{"name":"Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine","volume":"20 4","pages":"519-29"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jam.2007.0625","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27191721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

Characterization of deposition from nasal spray devices using a computational fluid dynamics model of the human nasal passages. 使用人类鼻腔通道的计算流体动力学模型表征鼻腔喷雾装置的沉积。

Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine Pub Date : 2007-01-01 DOI: 10.1089/jam.2006.0531

Julia S Kimbell, Rebecca A Segal, Bahman Asgharian, Brian A Wong, Jeffry D Schroeter, Jeremy P Southall, Colin J Dickens, Geoff Brace, Frederick J Miller

{"title":"Characterization of deposition from nasal spray devices using a computational fluid dynamics model of the human nasal passages.","authors":"Julia S Kimbell, Rebecca A Segal, Bahman Asgharian, Brian A Wong, Jeffry D Schroeter, Jeremy P Southall, Colin J Dickens, Geoff Brace, Frederick J Miller","doi":"10.1089/jam.2006.0531","DOIUrl":"https://doi.org/10.1089/jam.2006.0531","url":null,"abstract":"Many studies suggest limited effectiveness of spray devices for nasal drug delivery due primarily to high deposition and clearance at the front of the nose. Here, nasal spray behavior was studied using experimental measurements and a computational fluid dynamics model of the human nasal passages constructed from magnetic resonance imaging scans of a healthy adult male. Eighteen commercially available nasal sprays were analyzed for spray characteristics using laser diffraction, high-speed video, and high-speed spark photography. Steadystate, inspiratory airflow (15 L/min) and particle transport were simulated under measured spray conditions. Simulated deposition efficiency and spray behavior were consistent with previous experimental studies, two of which used nasal replica molds based on this nasal geometry. Deposition fractions (numbers of deposited particles divided by the number released) of 20- and 50-microm particles exceeded 90% in the anterior part of the nose for most simulated conditions. Predicted particle penetration past the nasal valve improved when (1) the smaller of two particle sizes or the lower of two spray velocities was used, (2) the simulated nozzle was positioned 1.0 rather than 0.5 or 1.5 cm into the nostril, and (3) inspiratory airflow was present rather than absent. Simulations also predicted that delaying the appearance of normal inspiratory airflow more than 1 sec after the release of particles produced results equivalent to cases in which no inspiratory airflow was present. These predictions contribute to more effective design of drug delivery devices through a better understanding of the effects of nasal airflow and spray characteristics on particle transport in the nose.","PeriodicalId":14878,"journal":{"name":"Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine","volume":"20 1","pages":"59-74"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jam.2006.0531","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26629376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 144

Comparison of two approaches for treating cascade impaction mass balance measurements. 处理级联撞击质量平衡测量的两种方法的比较。

Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine Pub Date : 2007-01-01 DOI: 10.1089/jam.2007.0609

Bruce Wyka, Terrence Tougas, Jolyon Mitchell, Helen Strickland, David Christopher, Svetlana Lyapustina

{"title":"Comparison of two approaches for treating cascade impaction mass balance measurements.","authors":"Bruce Wyka, Terrence Tougas, Jolyon Mitchell, Helen Strickland, David Christopher, Svetlana Lyapustina","doi":"10.1089/jam.2007.0609","DOIUrl":"https://doi.org/10.1089/jam.2007.0609","url":null,"abstract":"The multistage cascade impactor (CI) is the most appropriate tool for measuring the aero-dynamic particle size distribution (APSD) of active pharmaceutical ingredient(s) (API) in the aerosol from an orally inhaled drug product. It is possible to determine the total emitted mass per actuation of the inhaler by summing the individual component results obtained when determining APSD. The determination of total mass per actuation recovered from the CI components (or \"mass balance\" [MB]) has inherently lower precision than that of a delivered dose (DD) determination. An FDA draft guidance for industry has proposed using CI-determined MB as part of the product specification, with acceptance criteria of +/-15% of the label claim (LC) dosage. We propose instead that MB be used to assess whether the CI measurement of APSD is reliable. Two multitiered test schemes for MB are evaluated that allow for retests to accommodate the variability of the MB measurement. We provide statistical evaluations of both test schemes by using operating characteristic (OC) curves. We find that a two-tiered procedure with broader acceptance criteria but limited opportunity for investigating and retesting MB failure results in a greater risk of rejection of good batches (\"false positive\" error) without the commensurate reduction in the risk of passing unacceptable batches (\"false negative\" error). In contrast, a three-tiered procedure with narrower acceptance criteria, but more opportunity to check for potential CI system malfunction/method misapplication and to rerun the CI test, provides a compromise that enables the MB measurement to be used without significantly increasing the probability of false positive errors.","PeriodicalId":14878,"journal":{"name":"Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine","volume":"20 3","pages":"236-56"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jam.2007.0609","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40993044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

IL-1 receptor antagonist as an aerosol in inflammation. IL-1受体拮抗剂在炎症中的气溶胶作用。

Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine Pub Date : 2007-01-01 DOI: 10.1089/jam.2007.0576

Alexander M Ischenko, Boris P Nikolaev, Tatiana V Kotova, Eugeny V Vorobeychikov, Velentina G Konusova, Ludmila Y Yakovleva

{"title":"IL-1 receptor antagonist as an aerosol in inflammation.","authors":"Alexander M Ischenko, Boris P Nikolaev, Tatiana V Kotova, Eugeny V Vorobeychikov, Velentina G Konusova, Ludmila Y Yakovleva","doi":"10.1089/jam.2007.0576","DOIUrl":"https://doi.org/10.1089/jam.2007.0576","url":null,"abstract":"The feasibility of efficient aerosol delivery of the human IL-1 receptor antagonist (IL-1Ra) for reduction of acute lung inflammation was demonstrated in a mouse model study. The therapeutic efficacy of dry powder formulations PM(2), PM(10) of IL-1Ra was studied at nonforced inhalation in an aerosol chamber using the DPI \"Spinhaler\". Micronized powder formulations for insufflation were produced by air-jet milling. The anti-inflammatory effect of IL-Ra preparation was assessed by differential cell counts and biochemical composition of bronchoalveolar lavage (BAL). Reactive oxygen species (ROS), metabolic parameters of BAL (pH, redox potential, total protein, and lactate), and morphological lung changes were investigated by methods of luminol-dependent chemoluminescence, electrochemistry, microscopy, optical, and NMR spectroscopy. Inhalation of IL-1Ra aerosol ensured the systemic absorption of IL-1Ra in the circulatory system and reduced the acute inflammatory response to intranasal lipopolysaccharide challenge. The inhaled anti-inflammatory dosage in aerosol administration appeared to be comparable with i.p. injection. The mechanism of positive action of pulmonary aerosol delivery of Il-Ra includes normalization of the oxidative activity of bronchoalveolar cells, prevention of neutrophil recruitment to the bronchoalveolar tract, and improving of cell respiration. The results were used to develop mathematical models of the anti-inflammatory effects of IL-Ra as functions of the doses and dispersion grades of IL-Ra preparations. Aerosol application of IL-Ra may be an apparent way for prophylactic treating of respiratory inflammation caused by bacterial antigens.","PeriodicalId":14878,"journal":{"name":"Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine","volume":"20 4","pages":"445-59"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jam.2007.0576","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27191208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4