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Lung drug deposition study

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https://www.readbyqxmd.com/read/28075194/aerosol-drug-delivery-during-noninvasive-positive-pressure-ventilation-effects-of-intersubject-variability-and-excipient-enhanced-growth
#1
Ross L Walenga, P Worth Longest, Anubhav Kaviratna, Michael Hindle
BACKGROUND: Nebulized aerosol drug delivery during the administration of noninvasive positive pressure ventilation (NPPV) is commonly implemented. While studies have shown improved patient outcomes for this therapeutic approach, aerosol delivery efficiency is reported to be low with high variability in lung-deposited dose. Excipient enhanced growth (EEG) aerosol delivery is a newly proposed technique that may improve drug delivery efficiency and reduce intersubject aerosol delivery variability when coupled with NPPV...
January 11, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/28060543/inhibition-of-the-kca3-1-channel-alleviates-established-pulmonary-fibrosis-in-a-large-animal-model
#2
Louise Organ, Barbara Bacci, Emmanuel Koumoundouros, Wayne G Kimpton, Chrishan S Samuel, Cameron J Nowell, Peter Bradding, Katy M Roach, Glen Westall, Jade Jaffar, Ken J Snibson
Idiopathic pulmonary fibrosis is a chronic progressive disease of increasing prevalence marked by poor prognosis and limited treatment options. Ca2+-activated KCa3.1 potassium channels have been shown to play a key role in the aberrant activation and responses to injury in both epithelial cells and fibroblasts, both considered key drivers in the fibrotic process of IPF. Pharmacological inhibition of IPF-derived fibroblasts is able to somewhat prevent TGF-βand bFGF-dependent profibrotic responses. In the current study, we investigated whether blockade of the KCa3...
January 6, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28028187/evaluating-the-effectiveness-of-written-dry-powder-inhaler-instructions-and-health-literacy-in-subjects-diagnosed-with-copd
#3
Hana J Alsomali, David L Vines, Brian D Stein, Ellen A Becker
BACKGROUND: Improper inhaler use results in decreased drug deposition in the lungs. The impact of health literacy and poor vision on the patient's ability to learn inhaler technique by reading instructions has not been confirmed. This study evaluated the effectiveness of learning inhaler technique from written instructions and the impact of health literacy for patients diagnosed with COPD who used a dry powder inhaler (DPI). METHODS: This pilot study recruited subjects diagnosed with COPD...
December 27, 2016: Respiratory Care
https://www.readbyqxmd.com/read/27993478/pharmaceutical-aerosols-deposition-patterns-from-a-dry-powder-inhaler-euler-lagrangian-prediction-and-validation
#4
Ravishekar Ravi Kannan, A J Przekwas, Narender Singh, Renishkumar Delvadia, Geng Tian, Ross Walenga
This study uses Computational Fluid Dynamics (CFD) to predict, analyze and validate the deposition patterns in a human lung for a Budesonide drug delivered from the Novolizer Dry Powder Inhaler device. We used a test case of known deposition patterns to validate our computational Euler Lagrangian-based deposition predictions. Two different lung models are used: (i) a basic ring-less trachea model and (ii) an advanced Human Zygote5 model. Unlike earlier attempts, the current simulations do not include the device in the computational domain...
December 16, 2016: Medical Engineering & Physics
https://www.readbyqxmd.com/read/27991644/pulmonary-surfactant-protein-sp-d-opsonises-carbon-nanotubes-and-augments-their-phagocytosis-and-subsequent-pro-inflammatory-immune-response
#5
Kirsten M Pondman, Basudev Paudyal, Robert B Sim, Anuvinder Kaur, Lubna Kouser, Anthony G Tsolaki, Lucy A Jones, Carolina Salvador-Morales, Haseeb A Khan, Bennie Ten Haken, Gudrun Stenbeck, Uday Kishore
Carbon nanotubes (CNTs) are increasingly being developed for use in biomedical applications, including drug delivery. One of the most promising applications under evaluation is in treating pulmonary diseases such as tuberculosis. Once inhaled or administered, the nanoparticles are likely to be recognised by innate immune molecules in the lungs such as hydrophilic pulmonary surfactant proteins. Here, we set out to examine the interaction between surfactant protein D (SP-D), a key lung pattern recognition molecule and CNTs, and possible downstream effects on the immune response via macrophages...
January 19, 2017: Nanoscale
https://www.readbyqxmd.com/read/27989858/aerosolizable-modified-release-particles-of-montelukast-improve-retention-and-availability-of-the-drug-in-the-lungs
#6
Brijeshkumar Patel, Jahidur Rashid, Fakhrul Ahsan
Montelukast, a cysteinyl leukotriene receptor antagonist available as oral tablets, is used as a second-line therapy in asthma. In this study, we sought to enhance the availability of montelukast in the lungs by encapsulating the drug in poly (lactide-co-glycolic acid)-based (PLGA) respirable large porous particles. We determined the oral and lung specific availability of montelukast by assessing metabolic stability of the drug in the lung and liver homogenates, respectively. We similarly measured the oral and inhalational bioavailability by monitoring the pharmacokinetics and disposition of the drug in live animals...
October 27, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27979017/inhalation-devices-delivery-systems-and-patient-technique
#7
Harold S Nelson
BACKGROUND: In real-life clinical settings, physicians often consider the properties of various inhaled corticosteroids (ICSs), but typically little consideration is given to the properties of different inhalers and formulations. OBJECTIVE: To discuss the effects of inhalation devices and user technique on efficacy, safety, and adherence with the aim of improving asthma management. METHODS: Relevant publications were selected to augment discussion...
December 2016: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/27977216/inhalation-of-respirable-crystalline-rifapentine-particles-induces-pulmonary-inflammation
#8
Thaigarajan Parumasivam, Anneliese S Ashhurst, Gayathri Nagalingam, Warwick J Britton, Hak-Kim Chan
Rifapentine is an anti-tuberculosis (anti-TB) drug with a prolonged half-life, but oral delivery results in low concentrations in the lungs because of its high binding (98%) to plasma proteins. We have shown that inhalation of crystalline rifapentine overcomes the limitations of oral delivery by significantly enhancing and prolonging the drug concentration in the lungs. The delivery of crystalline particles to the lungs may promote inflammation. This in vivo study characterizes the inflammatory response caused by pulmonary deposition of the rifapentine particles...
January 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27968887/infection-prevention-with-natural-protein-based-coating-on-the-surface-of-foley-catheters-a-randomised-controlled-clinical-trial
#9
Peng Zhao, Qijing Chen, Chao Lin, Zhaofen Lin, Liang Chang, Xiaoping Shao, Yueming Li, Jiangong Zhang, Zhongpeng Fan, Xuejun Wen
BACKGROUND: Health-care-associated infections characterised by antibiotic drug resistance are a global medical challenge that claims billions of dollars of health-care expenditure. Bacterial adhesion and subsequent formation of biofilms on catheters and tubes are the primary mechanisms through which these infections are initiated and propagated. We tested the efficacy and safety for clinical treatment of a coating based on natural protein, in which immunogenicity was eliminated through physical plasticising, applied to the surfaces of medical devices to inhibit bacterial adhesion...
October 2016: Lancet
https://www.readbyqxmd.com/read/27934123/aspects-of-quantitation-in-mass-spectrometry-imaging-investigated-on-cryo-sections-of-spiked-tissue-homogenates
#10
Heidi Toft Hansen, Christian Janfelt
Internal standards have been introduced in quantitative mass spectrometry imaging in order to compensate for differences in intensities throughout an image caused by, for example, difference in ion suppression or analyte extraction efficiency. To test how well the internal standards compensate for differences in tissue types in, for example, whole-body imaging, a set of tissue homogenates of different tissue types (lung, liver, kidney, heart, and brain) from rabbit was spiked to the same concentration with the drug amitriptyline and imaged in the same experiment using isotope labeled amitriptyline as internal standard...
December 6, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/27921442/nebulized-antibiotics-in-mechanically-ventilated-patients-roadmap-and-challenges
#11
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...
January 2, 2017: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/27911474/is-chelation-therapy-efficient-for-the-treatment-of-intravenous-metallic-mercury-intoxication
#12
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 outcome, 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 2 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 times...
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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