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Lung drug deposition study

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https://www.readbyqxmd.com/read/28810543/atorvastatin-has-a-protective-effect-in-a-mouse-model-of-bronchial-asthma-through-regulating-tissue-transglutaminase-and-triggering-receptor-expressed-on-myeloid-cells-1-expression
#1
Ming-Wei Liu, Rong Liu, Hai-Ying Wu, Mei Chen, Min-Na Dong, Yun-Qiao Huang, Chun-Hai Zhang, Yin-Zhong Wang, Jing Xia, Yang Shi, Feng-Mei Xie, Hua Luo, Xin-Yuan Zhao, Wei Wei, Mei-Xian Su
Airway remodeling in asthma contributes to airway hyperreactivity, loss of lung function and persistent symptoms. Current therapies do not adequately treat the structural airway changes associated with asthma. Statin drugs have improved respiratory health and their therapeutic potential in asthma has been tested in clinical trials. However, the mechanism of action of statins in this context has remained elusive. The present study hypothesized that atorvastatin treatment of ovalbumin-exposed mice attenuates early features of airway remodeling via a mevalonate-dependent mechanism...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28799097/predicting-pulmonary-pharmacokinetics-from-in-vitro-properties-of-dry-powder-inhalers
#2
Sharvari Bhagwat, Uta Schilling, Mong-Jen Chen, Xiangyin Wei, Renishkumar Delvadia, Mohammad Absar, Bhawana Saluja, Günther Hochhaus
PURPOSE: The ability of two semi-mechanistic simulation approaches to predict the systemic pharmacokinetics (PK) of inhaled corticosteroids (ICSs) delivered via dry powder inhalers (DPIs) was assessed for mometasone furoate, budesonide and fluticasone propionate. METHODS: Both approaches derived the total lung doses and the central to peripheral lung deposition ratios from clinically relevant cascade impactor studies, but differed in the way the pulmonary absorption rate was derived...
August 10, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28783251/safety-and-efficacy-of-allogeneic-lung-spheroid-cells-in-a-mismatched-rat-model-of-pulmonary-fibrosis
#3
Jhon Cores, M Taylor Hensley, Kathryn Kinlaw, S Michaela Rikard, Phuong-Uyen Dinh, Dipti Paudel, Junnan Tang, Adam C Vandergriff, Tyler A Allen, Yazhou Li, Jianhua Liu, Bo Niu, Yuepeng Chi, Thomas Caranasos, Leonard J Lobo, Ke Cheng
Idiopathic pulmonary fibrosis is a devastating interstitial lung disease characterized by the relentless deposition of extracellular matrix causing lung distortions and dysfunctions. The prognosis after detection is merely 3-5 years and the only two Food and Drug Administration-approved drugs treat the symptoms, not the disease, and have numerous side effects. Stem cell therapy is a promising treatment strategy for pulmonary fibrosis. Current animal and clinical studies focus on the use of adipose or bone marrow-derived mesenchymal stem cells...
August 7, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28777013/investigational-drugs-for-idiopathic-pulmonary-fibrosis
#4
Francesco Varone, Giuliano Montemurro, Francesco Macagno, Mariarosaria Calvello, Emanuele Conte, Enrica Intini, Bruno Iovene, Paolo Maria Leone, Pier-Valerio Mari, Luca Richeldi
IPF is a specific form of chronic fibrosing interstitial pneumonia of unknown cause, characterized by progressive worsening in lung function and an unfavorable prognosis. Current concepts on IPF pathogenesis are based on a dysregulated wound healing response, leading to an over production of extracellular matrix. Based on recent research however, several other mechanisms are now proposed as potential targets for novel therapeutic strategies. Areas covered: This review analyzes the current investigational strategies targeting extracellular matrix deposition, tyrosine-kinase antagonism, immune and autoimmune response, and cell-based therapy...
August 10, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28757441/exogenous-nitric-oxide-enhances-the-prophylactic-effect-of-aminoguanidine-a-preferred-inos-inhibitor-on-bleomycin-induced-fibrosis-in-the-lung-implications-for-the-direct-roles-of-the-no-molecule-in-vivo
#5
Chao Chen, Xiao-Jing Yun, Li-Ze Liu, Hong Guo, Lian-Feng Liu, Xiao-Ling Chen
OBJECTIVE: Inducible nitric oxide synthase (iNOS) aggravates and endothelial nitric oxide synthase (eNOS) ameliorates fibrosis in the lung. Our previous study demonstrated that aminoguanidine (AG), a preferred iNOS inhibitor, prevents bleomycin-induced injury and fibrosis in the lung. The diethylenetriamine nitric oxide adduct (DETA/NO) is a slow-release NO donor. Here, to clarify the exact role of the nitric oxide (NO) molecule in the pathogenesis of pulmonary fibrosis in vivo, we observed the effects of inhalation of aerosolized DETA/NO on fibrosis in the lungs of bleomycin-exposed rats with AG treatment, including the effects on the myofibroblast number, collagen deposition, peroxynitrite anion (ONOO(-)) formation, and injury in the lung...
July 27, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28735415/cfd-simulation-of-aerosol-delivery-to-a-human-lung-via-surface-acoustic-wave-nebulization
#6
Morteza Yousefi, Oveis Pourmehran, Mofid Gorji-Bandpy, Kiao Inthavong, Leslie Yeo, Jiyuan Tu
Administration of drug in the form of particles through inhalation is generally preferable in the treatment of respiratory disorders. Conventional inhalation therapy devices such as inhalers and nebulizers, nevertheless, suffer from low delivery efficiencies, wherein only a small fraction of the inhaled drug reaches the lower respiratory tract. This is primarily because these devices are not able to produce a sufficiently fine drug mist that has aerodynamic diameters on the order of a few microns. This study employs computational fluid dynamics to investigate the transport and deposition of the drug particles produced by a new aerosolization technique driven by surface acoustic waves (SAWs) into an in silico lung model geometrically reconstructed using computed tomography scanning...
July 22, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28732821/optimizing-inhalation-technique-using-web-based-videos-in-obstructive-lung-diseases
#7
Tobias Müller, Annegret Müller, Christian Hübel, Verena Knipel, Wolfram Windisch, Christian Gabriel Cornelissen, Michael Dreher
BACKGROUND: Inhaled agents are widely used in the treatment of chronic airway diseases. Correct technique is required to ensure appropriate drug deposition, but poor technique is common. This study investigated whether inhalation technique could be improved by patient training using short videos from the German Airway League. METHODS: Outpatients from a university hospital respiratory clinic who had incorrect inhalation technique were asked to demonstrate this again immediately after viewing the training videos, and after 4-8 weeks' follow-up...
August 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/28684908/%C3%AE-bisabolol-loaded-lipid-core-nanocapsules-reduce-lipopolysaccharide-induced-pulmonary-inflammation-in-mice
#8
Ana Paula L D'Almeida, Maria T Pacheco de Oliveira, Éverton T de Souza, Diego de Sá Coutinho, Bianca T Ciambarella, Cristiano R Gomes, Thatiana Terroso, Sílvia S Guterres, Adriana R Pohlmann, Patrícia Mr Silva, Marco A Martins, Andressa Bernardi
Acute respiratory distress syndrome (ARDS) is a severe clinical condition of respiratory failure due to an intense inflammatory response with different etiologies. Despite all efforts, therapy remains limited, and ARDS is still associated with high mortality and morbidity. Plants can provide a vast source of active natural products for the discovery of new drugs. α-bisabolol (α-bis), a constituent of the essential oil from chamomile, has elicited pharmacological interest. However, the molecule has some limitations to its biological application...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28656009/role-of-microbial-agents-in-pulmonary-fibrosis%C3%A2
#9
REVIEW
Ozioma S Chioma, Wonder P Drake
Pulmonary fibrosis is a form of lung disease that develops due to aberrant wound-healing following repeated alveoli injury in genetically susceptible individuals, resulting in chronic inflammation, excess deposition of the extracellular matrix components, mainly collagen, and scarring of lung tissue. In addition to irradiation, environmental agents such occupational inhalants, and chemotherapeutic agents, microbial agents also play a role in the etiology of the disease. While viruses have received the most attention, emerging evidence suggest that bacteria and fungi also play a part in the etiology of pulmonary fibrosis...
June 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28655664/protection-of-hydrophobic-amino-acids-against-moisture-induced-deterioration-in-the-aerosolization-performance-of-highly-hygroscopic-spray-dried-powders
#10
Jiaqi Yu, Hak-Kim Chan, Thomas Gengenbach, John A Denman
BACKGROUND: Inhalable particles containing amorphous form of drugs or excipients may absorb atmospheric moisture, causing powder aggregation and recrystallization, adversely affecting powder dispersion and lung deposition. The present study aims to explore hydrophobic amino acids for protection against moisture in spray-dried amorphous powders, using disodium cromoglycate (DSCG) as a model drug. MATERIALS AND METHODS: DSCG powders were produced by co-spray drying with isoleucine (Ile), valine (Val) and methionine (Met) in various concentrations (10, 20 and 40% w/w)...
June 24, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28647590/differences-in-the-coronal-proteome-acquired-by-particles-depositing-in-the-lungs-of-asthmatic-versus-healthy-humans
#11
Abhinav Kumar, Elif Melis Bicer, Paul Pfeffer, Marco P Monopoli, Kenneth A Dawson, Jonny Eriksson, Katarina Edwards, Steven Lynham, Matthew Arno, Annelie F Behndig, Anders Blomberg, Graham Somers, Dave Hassall, Lea Ann Dailey, Ben Forbes, Ian Mudway
Most inhaled nanomedicines in development are for the treatment of lung disease, yet little is known about their interaction with the respiratory tract lining fluids (RTLFs). Here we combined the use of nano-silica, as a protein concentrator, with label-free snapshot proteomics (LC-MS/MS; key findings confirmed by ELISA) to generate a quantitative profile of the RTLF proteome and provided insight into the evolved corona; information that may be used in future to improve drug targeting to the lungs by inhaled medicines...
June 22, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28646530/pirfenidone-reduces-subchondral-bone-loss-and-fibrosis-after-murine-knee-cartilage-injury
#12
Deva D Chan, Jun Li, Wei Luo, Dan N Predescu, Brian J Cole, Anna Plaas
Pirfenidone is an anti-inflammatory and anti-fibrotic drug that has shown efficacy in lung and kidney fibrosis. Because inflammation and fibrosis have been linked to the progression of osteoarthritis, we investigated the effects of oral Pirfenidone in a mouse model of cartilage injury, which results in chronic inflammation and joint-wide fibrosis in mice that lack hyaluronan synthase 1 (Has1(-/-) ) in comparison to wild-type. Femoral cartilage was surgically injured in wild-type and Has1(-/-) mice, and Pirfenidone was administered in food starting after 3 days...
June 23, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28645838/sensitivity-analysis-and-uncertainty-quantification-in-pulmonary-drug-delivery-of-orally-inhaled-pharmaceuticals
#13
Jun Lu, Jinxiang Xi, Joseph E Langenderfer
In spite of widespread use of modeling tools in inhalation dosimetry, it remains difficult to quantify the output uncertainties when subjected to various sources of input variability. This study aimed to develop a computational model that can quantify the input sensitivity and output uncertainty in pulmonary drug delivery by coupling probabilistic analysis package NESSUS with ANSYS Fluent. An image-based mouth-lung model was used to simulate the transport and deposition of drug particles and variability in particle size, density, and inhalation speed were considered...
June 20, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28641140/effect-of-c1-inh-on-ischemia-reperfusion-injury-in-a-porcine-limb-ex-vivo-perfusion-model
#14
Mai M Abdelhafez, Jane Shaw, Damian Sutter, Jonas Schnider, Yara Banz, Hansjörg Jenni, Esther Voegelin, Mihai A Constantinescu, Robert Rieben
Revascularization of an amputated limb within 4-6h is essential to avoid extensive ischemia/reperfusion (I/R) injury leading to vascular leakage, edema and tissue necrosis. I/R injury is a pathological inflammatory condition that occurs during reperfusion of an organ or tissue after prolonged ischemia. It is characterized by a complex crosstalk between endothelial cell activation and the activation of plasma cascades. Vasculoprotective pharmacological intervention to prevent I/R injury might be an option to prolong the time window between limb amputation and successful replantation...
June 19, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28636254/a-histological-and-reference-system-for-the-analysis-of-mouse-intervertebral-disc
#15
Vivian Tam, Wilson C W Chan, Victor Y L Leung, Kathryn S E Cheah, Kenneth M C Cheung, Daisuke Sakai, Matthew R McCann, Jake Bedore, Cheryle A Séguin, Danny Chan
A new scoring system based on histo-morphology of mouse intervertebral disc (IVD) was established to assess changes in different mouse models of IVD degeneration and repair. IVDs from mouse strains of different ages, transgenic mice, or models of artificially-induced IVD degeneration were assessed. Morphological features consistently observed in normal, and early/later stages of degeneration were categorised into a scoring system focused on nucleus pulposus (NP) and annulus fibrosus (AF) changes. "Normal NP" exhibited a highly cellularised cell mass that decreased with natural ageing and in disc degeneration...
June 21, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28629719/alpha-ketoglutarate-nanoparticles-a-potentially-effective-treatment-for-cyanide-poisoning
#16
Shaheen Sultana, Sushma Talegaonkar, Dhruv Kumar Nishad, Gaurav Mittal, F J Ahmad, Aseem Bhatnagar
The purpose of this research work was to prepare nanosized formulation of alpha ketoglutarate as dry powder inhaler for cyanide poisoning. Nanosizing can be approached by solid phase and liquid phase method. The different conditions encountered in both these approaches can greatly affect the particle characteristics. In this study milling and precipitation technique were compared to study their effect on α-KG particles characteristics. Differences in choice of stabilizers were observed between the two processing techniques...
June 16, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28602990/enhancement-in-in-vitro-anti-angiogenesis-activity-and-cytotoxicity-in-lung-cancer-cell-by-pectin-pvp-based-curcumin-particulates
#17
Dinanath Gaikwad, Rajnita Shewale, Vinit Patil, Dipak Mali, Uday Gaikwad, Namdeo Jadhav
The aim of this work was to prepare pectin-poly (vinyl pyrrolidone) [PVP] based curcumin particulates to enhance the anticancer potential of curcumin, solubility and allow its localized controlled release. Pectin-PVP based curcumin particulates (PECTIN-PVP CUR) were prepared by spray drying technique in different ratios and were evaluated for surface morphology, micromeritics, flowability, particle size, drug content, in vitro dissolution, inhalable fraction, anti-angiogenesis/angiolysis and cytotoxicity. Results of micromeritic properties, Carr's index, Hausner's ratio and angle of repose were satisfactory...
June 9, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28599855/impact-of-droplet-evaporation-rate-on-resulting-in-vitro-performance-parameters-of-pressurized-metered-dose-inhalers
#18
Poonam Sheth, Matthew R Grimes, Stephen W Stein, Paul B Myrdal
Pressurized metered dose inhalers (pMDIs) are widely used for the treatment of pulmonary diseases. The overall efficiency of pMDI drug delivery may be defined by in vitro parameters such as the amount of drug that deposits on the model throat and the proportion of the emitted dose that has particles that are sufficiently small to deposit in the lung (i.e., fine particle fraction, FPF). The study presented examines product performance of ten solution pMDI formulations containing a variety of cosolvents with diverse chemical characteristics by cascade impaction with three inlets (USP induction port, Alberta Idealized Throat, and a large volume chamber)...
August 7, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28584899/development-of-aerosol-phospholipid-microparticles-for-the-treatment-of-pulmonary-hypertension
#19
Sarah Brousseau, Zimeng Wang, Sweta K Gupta, Samantha A Meenach
Pulmonary arterial hypertension (PAH) is an incurable cardiovascular disease characterized by high blood pressure in the arteries leading from the heart to the lungs. Over two million people in the USA are diagnosed with PAH annually and the typical survival rate is only 3 years after diagnosis. Current treatments are insufficient because of limited bioavailability, toxicity, and costs associated with approved therapeutics. Aerosol delivery of drugs is an attractive approach to treat respiratory diseases because it increases localized drug concentration while reducing systemic side effects...
June 5, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28544857/new-treatment-directions-for-ipf-current-status-of-ongoing-and-upcoming-clinical-trials
#20
Francesco Macagno, Francesco Varone, Paolo Maria Leone, Pier-Valerio Mari, Loredana Panico, Ludovica Berardini, Luca Richeldi
The main objective of this review is to explore the wide and expanding field of new clinical trials in IPF. Recent trials have confirmed the efficacy of the approved drugs pirfenidone and nintedanib; nonetheless, the discovery of new biological pathways has opened new horizons in this field. Areas covered: New strategies against matrix deposition are under study and so is for the role of immunity and autoimmunity. Recent advances in the use of stem cells are opening new possibilities for the recovery of damaged lung tissues...
July 2017: Expert Review of Respiratory Medicine
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