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Lung drug deposition study

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https://www.readbyqxmd.com/read/27921442/nebulized-antibiotics-in-mechanically-ventilated-patients-roadmap-and-challenges
#1
G Poulakou, G Siakallis, S Tsiodras, A Arfaras Melainis, G Dimopoulos
Nebulized antibiotics use has become common practice in the therapeutics of pneumonia in cystic fibrosis patients. There is an increasing interest in their use for respiratory infections in mechanically ventilated (MV) patients in order to a) overcome pharmacokinetic issues in the lung compartment with traditional systemic antibiotic use and b) prevent the emergence of multi-drug-resistant (MDR) pathogens. Areas covered: The beneficial effects of antibiotic nebulization in MV patients e.g. increasing efficacy, reduced toxicity and prevention of resistance are described...
December 6, 2016: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/27911474/is-chelation-therapy-efficient-for-the-treatment-of-intravenous-metallic-mercury-intoxication
#2
Daniela Pelclova, Stepanka Vlckova, Ondrej Bezdicek, Manuela Vaneckova, Pavel Urban, Petr Ridzon, Pavel Diblik, Tomas Navratil, Pavlina Klusackova, Kamil Vlcek, Olga Benesova, Pavel Trestik, Jiri Homolka, Sergey Zakharov
The efficacy of treatment for intravenous elemental mercury intoxication has not been fully studied with regard to clinical outcomes, and treatment recommendations vary. We treated a 41-year-old man with a history of drug abuse and depression who attempted suicide using 1 mL (13.53 g) metallic Hg i.v. He was admitted to the hospital two months later for dyspnoea and thoracic pain and was diagnosed with pneumonia. Hg deposits were seen in the lungs and extra-pulmonary organs. His blood level (372 μg/L) exceeded the population level of 5 μg/L by more than 70-fold...
December 2, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27853177/difference-in-resistance-to-humidity-between-commonly-used-dry-powder-inhalers-an-in-vitro-study
#3
Christer Janson, Thomas Lööf, Gunilla Telg, Georgios Stratelis, Folke Nilsson
Multi-dose dry powder inhalers (DPIs) are commonly used in asthma and chronic obstructive lung disease (COPD) treatment. A disadvantage is their sensitivity to humidity. In real life, DPIs are periodically exposed to humid conditions, which may affect aerosol characteristics and lung deposition. This study compared DPI aerosol performance after exposure to humidity. Budesonide (BUD) inhalers (Turbuhaler; Novolizer; Easyhaler) and budesonide/formoterol (BUD/FORM) inhalers (Turbuhaler; Spiromax; Easyhaler) were stored in 75% relative humidity (RH) at both ambient temperature and at -0 °C...
November 17, 2016: NPJ Primary Care Respiratory Medicine
https://www.readbyqxmd.com/read/27836120/computationally-efficient-analysis-of-particle-transport-and-deposition-in-a-human-whole-lung-airway-model-part-ii-dry-powder-inhaler-application
#4
Arun V Kolanjiyil, Clement Kleinstreuer, Ruxana T Sadikot
Pulmonary drug delivery is becoming a favored route for administering drugs to treat both lung and systemic diseases. Examples of lung diseases include asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD) as well as respiratory distress syndrome (ARDS) and pulmonary fibrosis. Special respiratory drugs are administered to the lungs, using an appropriate inhaler device. Next to the pressurized metered-dose inhaler (pMDI), the dry powder inhaler (DPI) is a frequently used device because of the good drug stability and a minimal need for patient coordination...
November 3, 2016: Computers in Biology and Medicine
https://www.readbyqxmd.com/read/27825470/monoclonal-igm-related-al-amyloidosis
#5
REVIEW
Paolo Milani, Giampaolo Merlini
Monoclonal immunoglobulin M (IgM)-related light chain (AL) amyloidosis, which accounts for 5%-7% of all AL amyloidosis cases, is a distinct clinical entity that poses specific challenges to clinicians. Several studies reported that although there is a substantial overlap, the pattern of organ involvement is peculiar, with higher frequencies of lung, lymph nodes, and peripheral nervous system involvement. A recent collaborative study from three European referral centers, defined that cardiac involvement, advanced Mayo disease stage, neuropathic, and liver involvement were independent factors that had impact on survival in IgM-AL amyloidosis patients...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27803453/evaluation-of-proinflammatory-cytokines-and-adverse-events-in-healthy-volunteers-upon-inhalation-of-antituberculosis-drugs
#6
Teerapol Srichana, Chaveewan Ratanajamit, Siwasak Juthong, Tan Suwandecha, Nisa Laohapojanart, Petchawan Pungrassami, Alwar Ramanujam Padmavathi
Inhalation therapy is a promising drug delivery approach for tuberculosis treatment. However, there is always concern about the safety of the dosage form by inhalation as it may induce inflammation. Developing a new dosage form for inhalation must include tests for its safety especially for the tumor necrosis factor (TNF)-α and interleukine (IL)-1β. The safety of four anti-tuberculosis (anti-TB) drugs administered via inhalation was assessed in healthy volunteers. Four anti-TB drugs; isoniazid, rifampicin, pyrazinamide and levofloxacin were prepared as dry powder and evaluated for uniformity of delivered dose and in vitro drug deposition...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27774309/microparticulate-nanoparticulate-powders-of-a-novel-nrf2-activator-and-an-aerosol-performance-enhancer-for-pulmonary-delivery-targeting-the-lung-nrf2-keap-1-pathway
#7
Priya Muralidharan, Don Hayes, Stephen M Black, Heidi M Mansour
This systematic and comprehensive study reports for the first time on the successful rational design of advanced inhalable therapeutic dry powders containing dimethyl fumarate, a first-in-class Nrf2 activator drug to treat pulmonary inflammation, using particle engineering design technology for targeted delivery to the lungs as advanced spray dried (SD) one-component DPIs. In addition, two-component co-spray dried (co-SD) DMF:D-Man DPIs with high drug loading were successfully designed for targeted lung delivery as advanced DPIs using organic solution advanced spray drying in closed mode...
2016: Molecular Systems Design & Engineering
https://www.readbyqxmd.com/read/27725433/investigation-of-appropriate-inhalation-technique-for-mometasone-furoate-dry-powder-inhaler
#8
Haruko Yokoyama, Kanako Ito, Hirokazu Mihashi, Yasuyuki Shiraishi, Risa Takayanagi, Yasuhiko Yamada
The aim of this study was to establish an appropriate inhalation method with a mometasone furoate dry powder inhaler (MF-DPI). Utilizing a tone-based inhalation training device, we investigated the maximum peak inspiratory flow rate time (Tmax PIFR) and peak inspiratory flow rate (PIFR) to determine whether either had an influence on lung deposition with use of an MF-DPI. A low tone indicated a PIFR of 28 L/min and a high tone that of 40 L/min, while 60 L/min was considered to be the standard. We established an inhalation profile in consideration of a human inhalation pattern, in which Tmax PIFR was set at 0...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27724909/a-systematic-review-of-comparative-studies-of-tiotropium-respimat%C3%A2-and-tiotropium-handihaler%C3%A2-in-patients-with-chronic-obstructive-pulmonary-disease-does-inhaler-choice-matter
#9
Ronald Dahl, Alan Kaplan
BACKGROUND: In many countries worldwide, the long-acting anticholinergic drug tiotropium is available as a dry powder formulation delivered by means of the HandiHaler® inhalation device and as an aqueous solution delivered via the Respimat® Soft Mist™ Inhaler. Tiotropium HandiHaler® is a single-dose, dry powder, breath-actuated inhaler that provides delivered doses and lung deposition of tiotropium that are, over a wide range, not influenced by the severity of chronic obstructive pulmonary disease (COPD)...
October 11, 2016: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/27704718/hydamtiq-a-selective-parp-1-inhibitor-improves-bleomycin-induced-lung-fibrosis-by-dampening-the-tgf-%C3%AE-smad-signalling-pathway
#10
Laura Lucarini, Mariaconcetta Durante, Cecilia Lanzi, Alessandro Pini, Giulia Boccalini, Laura Calosi, Flavio Moroni, Emanuela Masini, Guido Mannaioni
Idiopathic pulmonary fibrosis is a severe disease characterized by excessive myofibroblast proliferation, extracellular matrix and fibrils deposition, remodelling of lung parenchyma and pulmonary insufficiency. Drugs able to reduce disease progression are available, but therapeutic results are unsatisfactory; new and safe treatments are urgently needed. Poly(ADP-ribose) polymerases-1 (PARP-1) is an abundant nuclear enzyme involved in key biological processes: DNA repair, gene expression control, and cell survival or death...
October 4, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27695294/combined-computational-and-experimental-studies-of-molecular-interactions-of-albuterol-sulfate-with-bovine-serum-albumin-for-pulmonary-drug-nanoparticles
#11
Shao-Hui Lin, Wei Cui, Gui-Ling Wang, Shuai Meng, Ying-Chun Liu, Hong-Wei Jin, Liang-Ren Zhang, Ying Xie
Albumin-based nanoparticles (NPs) are a promising technology for developing drug-carrier systems, with improved deposition and retention profiles in lungs. Improved understanding of these drug-carrier interactions could lead to better drug-delivery systems. The present study combines computational and experimental methods to gain insights into the mechanism of binding of albuterol sulfate (AS) to bovine serum albumin (BSA) on the molecular level. Molecular dynamics simulation and surface plasmon resonance spectroscopy were used to determine that there are two binding sites on BSA for AS: the first of which is a high-affinity site corresponding to AS1 and the second of which appears to represent the integrated functions of several low-affinity sites corresponding to AS2, AS3, and AS8...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27685186/autologous-co-culture-of-primary-human-alveolar-macrophages-and-epithelial-cells-for-investigating-aerosol-medicines-part-ii-evaluation-of-il-10-loaded-microparticles-for-the-treatment-of-lung-inflammation
#12
Marius Hittinger, Nico Alexander Mell, Hanno Huwer, Brigitta Loretz, Nicole Schneider-Daum, Claus-Michael Lehr
Acute respiratory distress syndrome is linked to inflammatory processes in the human lung. The aim of this study was to mimic in vitro the treatment of lung inflammation by using a cell-based human autologous co-culture model. As a potential trial medication, we developed a pulmonary dry powder formulation loaded with interleukin-10 (IL-10), a potent anti-inflammatory cytokine. The inflammatory immune response was stimulated by lipopolysaccharide. The co-culture was combined with the Pharmaceutical Aerosol Deposition Device on Cell Cultures )PADDOCC), to deposit the IL-10-loaded microparticles on the inflamed co-culture model at the air-liquid interface...
September 2016: Alternatives to Laboratory Animals: ATLA
https://www.readbyqxmd.com/read/27685185/autologous-co-culture-of-primary-human-alveolar-macrophages-and-epithelial-cells-for-investigating-aerosol-medicines-part-i-model-characterisation
#13
Marius Hittinger, Julia Janke, Hanno Huwer, Regina Scherließ, Nicole Schneider-Daum, Claus-Michael Lehr
The development of new formulations for pulmonary drug delivery is a challenge on its own. New in vitro models which address the lung are aimed at predicting and optimising the quality, efficacy and safety of inhaled drugs, to facilitate the more rapid translation of such products into the clinic. Reducing the complexity of the in vivo situation requires that such models reproducibly reflect essential physiological factors in vitro. The choice of cell types, culture conditions and the experimental set-up, can affect the outcome and the relevance of a study...
September 2016: Alternatives to Laboratory Animals: ATLA
https://www.readbyqxmd.com/read/27590145/jnk-inhibition-reduces-lung-remodeling-and-pulmonary-fibrotic-systemic-markers
#14
Jos L J van der Velden, Ying Ye, James D Nolin, Sidra M Hoffman, David G Chapman, Karolyn G Lahue, Sarah Abdalla, Peng Chen, Yong Liu, Brydon Bennett, Nasreen Khalil, Donna Sutherland, William Smith, Gerald Horan, Mahmoud Assaf, Zebulun Horowitz, Rajesh Chopra, Randall M Stevens, Maria Palmisano, Yvonne M W Janssen-Heininger, Peter H Schafer
BACKGROUND: Lung remodeling and pulmonary fibrosis are serious, life-threatening conditions resulting from diseases such as chronic severe asthma and idiopathic pulmonary fibrosis (IPF). Preclinical evidence suggests that JNK enzyme function is required for key steps in the pulmonary fibrotic process. However, a selective JNK inhibitor has not been investigated in translational models of lung fibrosis with clinically relevant biomarkers, or in IPF patients. METHODS: The JNK inhibitor CC-930 was evaluated in the house dust mite-induced fibrotic airway mouse model, in a phase I healthy volunteer pharmacodynamic study, and subsequently in a phase II multicenter study of mild/moderate IPF (n = 28), with a 4-week, placebo-controlled, double-blind, sequential ascending-dose period (50 mg QD, 100 mg QD, 100 mg BID) and a 52-week open-label treatment-extension period...
December 2016: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/27552906/numerical-simulation-of-emitted-particle-characteristics-and-airway-deposition-distribution-of-symbicort-%C3%A2-turbuhaler-%C3%A2-dry-powder-fixed-combination-aerosol-drug
#15
Árpád Farkas, Ágnes Jókay, Imre Balásházy, Péter Füri, Veronika Müller, Gábor Tomisa, Alpár Horváth
One of the most widespread dry powder fixed combinations used in asthma and chronic obstructive pulmonary disease (COPD) management is Symbicort(®) Turbuhaler(®). The aim of this study was to simulate the deposition distribution of both components of this drug within the airways based on realistic airflow measurements. Breathing parameters of 25 healthy adults (11 females and 14 males) were acquired while inhaling through Turbuhaler(®). Individual specific emitted doses and particle size distributions of Symbicort(®) Turbuhaler(®) were determined...
October 10, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27522955/dilemmas-confusion-and-misconceptions-related-to-small-airways-directed-therapy
#16
Federico Lavorini, Søren Pedersen, Omar S Usmani
Over the last decade, there is increasing evidence that the small airways, i. e. airways <2 mm in internal diameter, contribute significantly to the pathophysiology and clinical expression of asthma and chronic obstructive pulmonary disease (COPD). The increased interest in small airways is, at least in part, a result of innovation in small-particle aerosol formulations that better target the distal lung and also advanced physiological methods of assessing small airway responses. Increasing the precision of drug deposition may improve targeting of specific diseases or receptor locations, decrease airway drug exposure and side effects, and thereby increase the efficiency and effectiveness of inhaled drug delivery...
August 11, 2016: Chest
https://www.readbyqxmd.com/read/27506512/controlled-drug-release-from-lung-targeted-nanocarriers-via-chemically-mediated-shell-permeabilisation
#17
Hanpeng Chen, Arcadia Woods, Ben Forbes, Stuart Jones
Nanocarriers can aid therapeutic agent administration to the lung, but controlling drug delivery from these systems after deposition in the airways can be problematic. The aim of this study was to evaluate if chemically mediated shell permeabilisation could help manipulate the rate and extent of nanocarrier drug release. Rifampicin was loaded into lipid shell (loading efficiency 41.0±11.4%, size 50nm) and polymer shell nanocarriers (loading efficiency 25.9±2.3%, size 250nm). The drug release at pH 7.4 (lung epithelial pH) and 4...
September 25, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27448179/ciprofloxacin-dry-powder-for-inhalation-in-patients-with-noncystic-fibrosis-bronchiectasis-or-chronic-obstructive-pulmonary-disease-and-in-healthy-volunteers
#18
Heino Stass, Johannes Nagelschmitz, Dominik Kappeler, Knut Sommerer, Claudius Kietzig, Boris Weimann
BACKGROUND: Ciprofloxacin dry powder for inhalation (Ciprofloxacin DPI) is in development as long-term intermittent therapy to reduce the frequency of acute exacerbations in noncystic fibrosis bronchiectasis (NCFB) patients with respiratory bacterial pathogens. There is no approved therapy in this indication. Reliable, reproducible lung deposition is a prerequisite for inhaled drugs. METHODS: In this phase I study, six patients with NCFB, six with chronic obstructive pulmonary disease (COPD), and 12 healthy volunteers (HVs), received one dose of (99m)Tc-Ciprofloxacin DPI 32...
July 22, 2016: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/27445817/measurements-of-deposition-lung-surface-area-and-lung-fluid-for-simulation-of-inhaled-compounds
#19
REVIEW
Eleonore Fröhlich, Annalisa Mercuri, Shengqian Wu, Sharareh Salar-Behzadi
Modern strategies in drug development employ in silico techniques in the design of compounds as well as estimations of pharmacokinetics, pharmacodynamics and toxicity parameters. The quality of the results depends on software algorithm, data library and input data. Compared to simulations of absorption, distribution, metabolism, excretion, and toxicity of oral drug compounds, relatively few studies report predictions of pharmacokinetics and pharmacodynamics of inhaled substances. For calculation of the drug concentration at the absorption site, the pulmonary epithelium, physiological parameters such as lung surface and distribution volume (lung lining fluid) have to be known...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27343696/liraglutide-loaded-poly-lactic-co-glycolic-acid-microspheres-preparation-and-in-vivo-evaluation
#20
Junzi Wu, Gareth R Williams, Christopher Branford-White, Heyu Li, Yan Li, Li-Min Zhu
In this work, we sought to generate sustained-release injectable microspheres loaded with the GLP-1 analogue liraglutide. Using water-in-oil-in-water double emulsion methods, poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with liraglutide were prepared. The microspheres gave sustained drug release over 30days, with cumulative release of up to 90% reached in vitro. The microspheres were further studied in a rat model of diabetes, and their performance compared with a group given daily liraglutide injections...
September 20, 2016: European Journal of Pharmaceutical Sciences
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