Abstract:
BACKGROUND:Preclinical evaluation of new chemical entities (NCEs) designed to be administered by inhalation route requires lung administration to rodents, especially in the discovery phase. Different administration methods have been used until now, but more efforts are required to obtain controlled and reproducible lung deposition when only small amounts of neat powder material are available. METHODS:The PreciseInhale platform used in the present study enables well-controlled powder aerosol exposures with only small amounts of micronized neat material, providing data on inhalation pharmacokinetic (PK) of NCEs at a very early stage. The DustGun aerosol technology uses compressed air to generate a respirable aerosol from milligram-amounts of powder that is delivered to one animal at a time. The new methodology was used to investigate the inhalation PK and lung retention in the rat of the novel Chiesi PDE4 inhibitor CHF6001 in three exposure models of the PreciseInhale platform: nose-only, intratracheally intubated rat, and the isolated, ventilated, and perfused rat lung. Results were compared with data from two other pulmonary delivery systems commonly used in preclinical studies: liquid instillation and powder insufflation. RESULTS:Administration of micronized CHF6001 using the PreciseInhale system yielded lung exposures in the same range as the other tested devices, but the reproducibility in lung deposition was improved. The initial amount of CHF6001 in lungs at the first sampling time point was close to the predetermined target dose. Tracheal deposition with PreciseInhale (0.36 ± 0.22 μg) was significantly less than with other tested delivery systems: PennCentury (23.7 ± 3.2 μg) and Airjet (25.6 ± 7.2 μg). CONCLUSIONS:The PreciseInhale platform enabled the administration of CHF6001 powder with good accuracy and reproducibility, with low tracheal deposition. The new platform can be used at an early discovery stage to obtain inhalatory PK data for respirable aerosols of neat NCE powder without excipients and with minimal use of dry powder formulation work.
journal_name
J Aerosol Med Pulm Drug Delivjournal_title
Journal of aerosol medicine and pulmonary drug deliveryauthors
Fioni A,Selg E,Cenacchi V,Acevedo F,Brogin G,Gerde P,Puccini Pdoi
10.1089/jamp.2017.1369subject
Has Abstractpub_date
2018-02-01 00:00:00pages
61-70issue
1eissn
1941-2711issn
1941-2703journal_volume
31pub_type
杂志文章abstract:BACKGROUND:Predicting local lung tissue pharmacodynamic (PD) responses of inhaled drugs is a longstanding challenge related to the lack of experimental techniques to determine local free drug concentrations. This has prompted the use of physiologically based pharmacokinetic (PBPK) modeling to potentially predict local ...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2017.1436
更新日期:2019-02-01 00:00:00
abstract::Upper respiratory tract infections (URTIs), primarily acute rhinopharyngitis, tonsillitis, adenoiditis, and rhinosinusitis (RS), are major causes of morbidity in both children and adults of any age. In addition to the frequent occurrence of related medical problems and the associated socioeconomic costs, URTIs have a ...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,评审
doi:10.1089/jamp.2016.1300
更新日期:2017-02-01 00:00:00
abstract::Significant advances have been made in the last 50 years in developing safe and efficacious aerosol formulations for pulmonary delivery. The key to future innovation may lie at the interface between biology and particle engineering. Improved understanding of biological processes including particle clearance, cellular ...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,评审
doi:10.1089/jamp.2010.0838
更新日期:2010-12-01 00:00:00
abstract::Since the early 1960s, there has been a continuous evolution in scientific understanding regarding bioequivalence (BE) of oral dosage forms, intermittently punctuated by some breakthrough research findings and conceptual advances. The accumulated knowledge from this body of research has been translated into a sophisti...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,评审
doi:10.1089/jamp.2014.1144
更新日期:2014-12-01 00:00:00
abstract:BACKGROUND:Vitamin A (VA) is crucial for lung growth and development. In premature infants, inadequate VA levels are associated with an increased risk of bronchopulmonary dysplasia (BPD). Intramuscular VA supplementation has been shown to decrease the incidence of BPD, but is not widely used in the clinical setting due...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2017.1438
更新日期:2018-12-01 00:00:00
abstract:BACKGROUND:Particle size and velocity are two of the most significant factors that impact the deposition of pressurized metered-dose inhaler (pMDI) sprays in the mouth cavity. pMDIs are prominently used around the world in the treatment of patients suffering from a variety of lung diseases such as asthma and chronic ob...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2015.1264
更新日期:2016-12-01 00:00:00
abstract:BACKGROUND:Programmed cell death 4 (PDCD4), a protein that binds to eukaryotic initiation factor 4A (eIF4A), inhibits the initiation of translation. Although a number of tumor suppressors target transcription, Pdcd4 is the first suppressor targeting protein translation, and has also been suggested to function as a tumo...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2009.0778
更新日期:2010-10-01 00:00:00
abstract::Inhalation is a potentially viable route of administration for numerous agents. In diabetes mellitus, the need for frequent injections to achieve ideal glycemic control remains a significant limitation for initiating and complying with insulin therapy in a large number of patients. To overcome this barrier, inhaled in...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,评审
doi:10.1089/jamp.2011.0876
更新日期:2011-10-01 00:00:00
abstract::The use of gamma camera imaging following the inhalation of a radiolabel has been widely used by researchers to investigate the fate of inhaled aerosols. The application of two-dimensional (2D) planar gamma scintigraphy and single-photon emission computed tomography (SPECT) to the study of inhaled aerosols is discusse...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,评审
doi:10.1089/jamp.2011.0960
更新日期:2013-06-01 00:00:00
abstract:BACKGROUND:Dyspnea significantly impacts quality of life and is one of the most common symptoms in advanced illness. Systemically-administered opioids and benzodiazepines have been the most studied and utilized pharmacologic treatments for refractory dyspnea. Less attention has been given to the use of these medication...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,评审
doi:10.1089/jamp.2014.1136
更新日期:2015-02-01 00:00:00
abstract:BACKGROUND:Understanding the regional partition of deposition of inhaled particles within the lung is important for improving targeted delivery of inhaled aerosolized drugs. One factor affecting regional deposition is gravity. As the lung deforms under its own weight, changes in lung volume, in airway geometries, and i...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2014.1189
更新日期:2015-12-01 00:00:00
abstract:BACKGROUND:Computer modeling is used to predict inhaled aerosol deposition in the lung based on definition of the aerosol characteristics and the breathing pattern and airway anatomy of the subject. Validation of the models is limited by the lack of detailed experimental data. Three-dimensional imaging provides an oppo...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2014.1191
更新日期:2015-12-01 00:00:00
abstract:BACKGROUND:The Abbreviated Impactor Measurement (AIM) concept simplifies determination of aerodynamic size metrics for inhaler quality control testing. A similar approach is needed to compare in vitro particle size distribution metrics with human respiratory tract (HRT) deposition. METHODS:An abbreviated impactor base...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2011.0925
更新日期:2012-08-01 00:00:00
abstract::This article provides a concise review of the use of magnetic resonance imaging (MRI) for measurement of regional aerosol deposition in the lungs. Basic aspects of MRI and its use in lung imaging and measurement of regional ventilation are introduced. Imaging of hydrogen protons (water) and inhaled hyperpolarized gase...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,评审
doi:10.1089/jamp.2011.0897
更新日期:2012-04-01 00:00:00
abstract:PURPOSE:Many methods have been developed to evaluate dry powder inhalation techniques and their efficiency for disease control in asthma patients. However, it is difficult to apply these methods to clinical practice and research. In this study, we introduce a simple new method that can be applied to dry powder inhalati...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2014.1193
更新日期:2016-10-01 00:00:00
abstract::The success of inhalation therapy is not only dependent upon the pharmacology of the drugs being inhaled but also upon the site and extent of deposition in the respiratory tract. Similarly, the toxicity of environmental and industrial particulate matter is affected not only by the nature of the dust but also by the am...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2020.29029.cd
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND:Spiromax(®) is a novel dry powder inhaler for patients with asthma or chronic obstructive pulmonary disease (COPD). The studies presented here provide further data on attributes (in vitro dosing consistency with budesonide-formoterol (DuoResp) Spiromax; flow rates through empty versions of the Spiromax and T...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2015.1216
更新日期:2015-10-01 00:00:00
abstract:BACKGROUND:The unit dose dry powder inhaler (UD-DPI) is being considered as an alternative inhaler platform that, if developed, has the potential to improve access to inhaled respiratory medicines in developing countries. AIM:This study compared the systemic exposure of fluticasone furoate after delivery from the UD-D...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,随机对照试验
doi:10.1089/jamp.2016.1322
更新日期:2017-10-01 00:00:00
abstract:: Background: Salvia miltiorrhiza polyphenolic acid (SMPA) is effective in the treatment of cardiovascular diseases and currently it is administered orally or intravenously. However, SMPA is poorly absorbed orally and quickly eliminated in vivo. A long-term frequent intraveno...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2019.1538
更新日期:2020-04-01 00:00:00
abstract:: Background: Many countries have introduced a compulsory use of community masks for certain public areas during the SARS-CoV-2 pandemic. Different manufacturers offer reusable community masks in large quantities. The efficacy of these masks, however, is unknown. ...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2020.1635
更新日期:2020-09-23 00:00:00
abstract:BACKGROUND:Secondary lung infections are the primary cause of morbidity associated with cystic fibrosis lung disease. Aerosolized antibiotic inhalation is potentially advantageous but has limited effectiveness due to altered airway aerodynamics and deposition patterns that limit drug access to infected regions. One pot...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2017.1412
更新日期:2018-08-01 00:00:00
abstract:BACKGROUND:Mechanically ventilated patients commonly suffer from ventilator-associated pneumonia, hypoxemia, and other lower respiratory tract infection as a result of pathogen colonization and poor sputum clearance. Consequently, there is a high rate of morbidity and mortality in these patients. Dry powder mannitol in...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2016.1320
更新日期:2017-04-01 00:00:00
abstract:BACKGROUND:Small rodents continue to be the mainstay for the assessment of pharmacological and toxicological data of inhaled therapeutics. For meaningful interpretation of the results information about deposition of aerosol particles in the respiratory tract is warranted, but not trivial to obtain for animals with nose...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2011.0902
更新日期:2012-06-01 00:00:00
abstract::Antibiotic-resistant bacterial infections have renewed interest in finding substitute methods of treatment. The purpose of the present in vitro study was to investigate the possibility of respiratory delivery of a Burkholderia cepacia complex (BCC) bacteriophage by nebulized aerosol administration. Bacteriophages in i...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2008.0701
更新日期:2008-12-01 00:00:00
abstract:BACKGROUND:Inhaled corticosteroid (ICS) therapy has improved the quality of life (QOL) for many asthmatics and reduced mortality rates associated with asthma. However, some patients do not obtain therapeutic benefit despite satisfactory adherence. OBJECTIVES:To determine whether asthmatic patients were using ICS devic...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2010.0868
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND:To our knowledge, quantification of intranasal deposition of aerosol generated by Accuspray(™) (AS) in children has never been published. We hypothesized that deposition would vary significantly with age and with placement of the device within, or outside, of the nostril. METHODS:We tested these hypotheses ...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2014.1174
更新日期:2015-10-01 00:00:00
abstract:OBJECTIVES:This experimental study was conducted to determine the effects of training on inhaler technique and quality of life in patients with chronic obstructive pulmonary disease (COPD). METHODS:Among the patients who applied at the outpatient clinic of chest diseases between March 2009 and May 2010, a total of 69 ...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章,随机对照试验
doi:10.1089/jamp.2012.1017
更新日期:2013-12-01 00:00:00
abstract:: Background: The photo reflection method (PRM) is used to measure light reflected from particles released from dry powder inhalers (DPIs). This simple method depicts time trajectories of released drugs; however, it underestimates the number of particles at high peak inhalat...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2020.1610
更新日期:2020-11-04 00:00:00
abstract:BACKGROUND:The Respimat Soft Mist Inhaler is reported to generate an aerosol with low spray momentum and a small droplet size. However, the transport characteristics of the Respimat aerosol are not well understood. The objective of this study was to characterize the transport and deposition of an aerosol emitted from t...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2008.0708
更新日期:2009-06-01 00:00:00
abstract:BACKGROUND:Very little is known about the role of nasal morphology due to ethnic variation on particle deposition pattern in the sinonasal cavity. This preliminary study utilizes computational fluid dynamics (CFD) modeling to investigate sinonasal airway morphology and deposition patterns of intranasal sprayed particle...
journal_title:Journal of aerosol medicine and pulmonary drug delivery
pub_type: 杂志文章
doi:10.1089/jamp.2014.1205
更新日期:2016-04-01 00:00:00