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Pulmonary Drug deposition models

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https://www.readbyqxmd.com/read/29745565/-progress-in-numerical-simulation-and-experimental-study-on-inhalable-particles-deposition-in-human-respiratory-system
#1
REVIEW
Rong Li, Xiuguo Zhao, Yajun Liu, Xinxi Xu
Inhalable particles deposition in the human respiratory system is the main cause of many respiratory and cardiovascular diseases. It plays an important role in related disease prevention and treatment through establishing computer or external entity models to study rules of particle deposition. The paper summarized and analyzed the present research results of various inhalable particle deposition models of upper respiratory tract and pulmonary area, and expounded the application in the areas of disease inducement analysis, drug inhale treatment etc...
August 1, 2017: Sheng Wu Yi Xue Gong Cheng Xue za Zhi, Journal of Biomedical Engineering, Shengwu Yixue Gongchengxue Zazhi
https://www.readbyqxmd.com/read/29623041/an-adaptogen-withaferin-a-ameliorates-in-vitro-and-in-vivo-pulmonary-fibrosis-by-modulating-the-interplay-of-fibrotic-matricelluar-proteins-and-cytokines
#2
Swarna Bale, Pooladanda Venkatesh, Manoj Sunkoju, Chandraiah Godugu
Pulmonary fibrosis (PF) is chronic lung disease with only two FDA approved clinically available drugs, with limited safety profile. Inadequate therapy motivated us to explore the effect of vimentin inhibitor Withaferin A, as an anti-fibrotic agent against TGF-β1-induced in vitro fibrotic events and Bleomycin induced in vivo fibrosis with an emphasis on epithelial to mesenchymal transition (EMT), extracellular matrix deposition (ECM), inflammation, and angiogenesis. In vitro EMT and fibrotic events were induced by TGF-β1 in alveolar epithelial cells and human fetal lung fibroblasts followed by treatment with Withaferin A (0...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29486525/a-quasi-3d-compartmental-multi-scale-approach-to-detect-and-quantify-diseased-regional-lung-constriction-using-spirometry-data
#3
Ravishekar Ravi Kannan, Narender Singh, Andrzej Przekwas
Spirometry is a widely used pulmonary function test to detect the airflow limitations associated with various obstructive lung diseases, such as asthma, chronic obstructive pulmonary disease, and even obesity-related complications. These conditions arise due to the change in the airway resistance, alveolar compliance, and inductance values. Currently, zero-dimensional compartmental models are commonly used for calibrating these resistance, compliance, and inductance values, ie, solving the inverse spirometry problem...
May 2018: International Journal for Numerical Methods in Biomedical Engineering
https://www.readbyqxmd.com/read/29297393/substance-deposition-assessment-in-obstructed-pulmonary-system-through-numerical-characterization-of-airflow-and-inhaled-particles-attributes
#4
Antonios Lalas, Stavros Nousias, Dimitrios Kikidis, Aris Lalos, Gerasimos Arvanitis, Christos Sougles, Konstantinos Moustakas, Konstantinos Votis, Sylvia Verbanck, Omar Usmani, Dimitrios Tzovaras
BACKGROUND: Chronic obstructive pulmonary disease (COPD) and asthma are considered as the two most widespread obstructive lung diseases, whereas they affect more than 500 million people worldwide. Unfortunately, the requirement for detailed geometric models of the lungs in combination with the increased computational resources needed for the simulation of the breathing did not allow great progress to be made in the past for the better understanding of inflammatory diseases of the airways through detailed modelling approaches...
December 20, 2017: BMC Medical Informatics and Decision Making
https://www.readbyqxmd.com/read/29290827/local-intratracheal-delivery-of-perfluorocarbon-nanoparticles-to-lung-cancer-demonstrated-with-magnetic-resonance-multimodal-imaging
#5
Lina Wu, Xiaofei Wen, Xiance Wang, Chunan Wang, Xilin Sun, Kai Wang, Huiying Zhang, Todd Williams, Allen J Stacy, Junjie Chen, Anne H Schmieder, Gregory M Lanza, Baozhong Shen
Eighty percent of lung cancers originate as subtle premalignant changes in the airway mucosal epithelial layer of bronchi and alveoli, which evolve and penetrate deeper into the parenchyma. Liquid-ventilation, with perfluorocarbons (PFC) was first demonstrated in rodents in 1966 then subsequently applied as lipid-encapsulated PFC emulsions to improve pulmonary function in neonatal infants suffering with respiratory distress syndrome in 1996. Subsequently, PFC nanoparticles (NP) were extensively studied as intravenous (IV) vascular-constrained nanotechnologies for diagnostic imaging and targeted drug delivery applications...
2018: Theranostics
https://www.readbyqxmd.com/read/29243970/reactive-oxygen-species-damage-drives-cardiac-and-mitochondrial-dysfunction-following-acute-nano-titanium-dioxide-inhalation-exposure
#6
Cody E Nichols, Danielle L Shepherd, Quincy A Hathaway, Andrya J Durr, Dharendra Thapa, Alaeddin Abukabda, Jinghai Yi, Timothy R Nurkiewicz, John M Hollander
Nanotechnology offers innovation in products from cosmetics to drug delivery, leading to increased engineered nanomaterial (ENM) exposure. Unfortunately, health impacts of ENM are not fully realized. Titanium dioxide (TiO2 ) is among the most widely produced ENM due to its use in numerous applications. Extrapulmonary effects following pulmonary exposure have been identified and may involve reactive oxygen species (ROS). The goal of this study was to determine the extent of ROS involvement on cardiac function and the mitochondrion following nano-TiO2 exposure...
February 2018: Nanotoxicology
https://www.readbyqxmd.com/read/29197520/effects-of-pirfenidone-in-acute-and-sub-chronic-liver-fibrosis-and-an-initiation-promotion-cancer-model-in-the-mouse
#7
Oleksii Seniutkin, Shinji Furuya, Yu-Syuan Luo, Joseph A Cichocki, Hisataka Fukushima, Yuki Kato, Hiromi Sugimoto, Tomoko Matsumoto, Takeki Uehara, Ivan Rusyn
Liver fibrosis results from chronic tissue damage and excessive regeneration with accumulation of extracellular matrix proteins; it is a precursor of liver cirrhosis and hepatocellular carcinoma. Liver fibrosis treatments are primarily directed at inflammation, with few options to combat fibrogenesis. Pirfenidone is a drug approved for idiopathic pulmonary fibrosis and this study was focused on anti-fibrotic and anti-cancer potential of pirfenidone in the liver of male B6C3F1/J mice. In a dose-finding study, mice were treated with CCl4 (0...
January 15, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29180257/insights-on-animal-models-to-investigate-inhalation-therapy-relevance-for-biotherapeutics
#8
REVIEW
A Guillon, T Sécher, L A Dailey, L Vecellio, M de Monte, M Si-Tahar, P Diot, C P Page, N Heuzé-Vourc'h
Acute and chronic respiratory diseases account for major causes of illness and deaths worldwide. Recent developments of biotherapeutics opened a new era in the treatment and management of patients with respiratory diseases. When considering the delivery of therapeutics, the inhaled route offers great promises with a direct, non-invasive access to the diseased organ and has already proven efficient for several molecules. To assist in the future development of inhaled biotherapeutics, experimental models are crucial to assess lung deposition, pharmacokinetics, pharmacodynamics and safety...
January 30, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29163164/lassbio-897-reduces-lung-injury-induced-by-silica-particles-in-mice-potential-interaction-with-the-a-2a-receptor
#9
Vinicius F Carvalho, Tatiana P T Ferreira, Ana C S de Arantes, François Noël, Roberta Tesch, Carlos M R Sant'Anna, Eliezer J L Barreiro, Carlos A M Fraga, Patrícia M Rodrigues E Silva, Marco A Martins
Silicosis is a lethal fibro-granulomatous pulmonary disease highly prevalent in developing countries, for which no proper therapy is available. Among a small series of N -acylhydrazones, the safrole-derived compound LASSBio-897 (3-thienylidene-3, 4-methylenedioxybenzoylhydrazide) raised interest due to its ability to bind to the adenosine A2A receptor. Here, we evaluated the anti-inflammatory and anti-fibrotic potential of LASSBio-897, exploring translation to a mouse model of silicosis and the A2A receptor as a site of action...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29079338/advances-in-experimental-and-mechanistic-computational-models-to-understand-pulmonary-exposure-to-inhaled-drugs
#10
Per Bäckman, Sumit Arora, William Couet, Ben Forbes, Wilbur de Kruijf, Amrit Paudel
Prediction of local exposure following inhalation of a locally acting pulmonary drug is central to the successful development of novel inhaled medicines, as well as generic equivalents. This work provides a comprehensive review of the state of the art with respect to multiscale computer models designed to provide a mechanistic prediction of local and systemic drug exposure following inhalation. The availability and quality of underpinning in vivo and in vitro data informing the computer based models is also considered...
February 15, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29058607/aerosol-delivery-during-invasive-mechanical-ventilation-a-systematic-review
#11
Jonathan Dugernier, Stephan Ehrmann, Thierry Sottiaux, Jean Roeseler, Xavier Wittebole, Thierry Dugernier, François Jamar, Pierre-François Laterre, Gregory Reychler
BACKGROUND: This systematic review aimed to assess inhaled drug delivery in mechanically ventilated patients or in animal models. Whole lung and regional deposition and the impact of the ventilator circuit, the artificial airways and the administration technique for aerosol delivery were analyzed. METHODS: In vivo studies assessing lung deposition during invasive mechanical ventilation were selected based on a systematic search among four databases. Two investigators independently assessed the eligibility and the risk of bias...
October 21, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/29053080/aerosolizing-lipid-dispersions-enables-antibiotic-transport-across-mimics-of-the-lung-airway-surface-even-in-the-presence-of-pre-existing-lipid-monolayers
#12
Steven V Iasella, Amy Z Stetten, Timothy E Corcoran, Stephen Garoff, Todd M Przybycien, Robert D Tilton
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 potential strategy to better reach infected areas is to formulate aerosols with surfactants that induce surface tension gradients and drive postdeposition drug dispersal via Marangoni transport along the airway surface liquid (ASL)...
October 20, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/28972765/nanoparticles-of-ph-responsive-peg-doxorubicin-conjugates-interaction-with-an-in-vitro-model-of-lung-adenocarcinoma-and-their-direct-formulation-in-propellant-based-portable-inhalers
#13
K S V Krishna Rao, Qian Zhong, Elizabeth R Bielski, Sandro R P da Rocha
Pulmonary administration of polymer drug conjugates is of great potential clinical significance for treating lung cancer as such regimen significantly increases local drug concentrations while decreases systemic and local side effects. In this work, we demonstrate that nanoparticles prepared with methoxypoly(ethylene glycol) (mPEG)-doxorubicin (DOX) conjugates (mPEG-DOX) that have a pH-sensitive imine bond (Schiff base) can at the same time work as efficient carriers for DOX to kill cancer cells and also as a strategy to directly formulate nanoparticles in propellant-based inhalers...
November 6, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28942008/transport-of-ellipsoid-fibers-in-oscillatory-shear-flows-implications-for-aerosol-deposition-in-deep-airways
#14
Lihi Shachar-Berman, Yan Ostrovski, Alessandro De Rosis, Stavros Kassinos, Josué Sznitman
It is widely acknowledged that inhaled fibers, e.g. air pollutants and anthropogenic particulate matter, hold the ability to deposit deep into the lungs reaching the distal pulmonary acinar airways as a result of their aerodynamic properties; these particles tend to align with the flow and thus stay longer airborne relative to their spherical counterpart, due to higher drag forces that resist sedimentation. Together with a high surface-to-volume ratio, such characteristics may render non-spherical particles, and fibers in particular, potentially attractive airborne carriers for drug delivery...
February 15, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28940894/the-antiretroviral-agent-nelfinavir-mesylate-a-potential-therapy-for-systemic-sclerosis
#15
Cecilia G Sanchez, Steven V Molinski, Rafael Gongora, Meredith Sosulski, Taylor Fuselier, Stephen S MacKinnon, Debasis Mondal, Joseph A Lasky
OBJECTIVE: Transforming growth factor β1 (TGFβ1) is considered a key factor in fibrogenesis, and blocking TGFβ1 signaling pathways diminishes fibrogenesis in animal models. The objective of this study was to determine whether nelfinavir mesylate (NFV), a drug approved by the Food and Drug Administration (FDA) for treating HIV infection, could be repurposed to treat pulmonary fibrosis in patients with systemic sclerosis (SSc). METHODS: Normal human lung, ventricular, and skin fibroblasts as well as lung fibroblasts from SSc patients were used to determine the effects of NFV on fibroblast-to-myofibroblast differentiation mediated by TGFβ1...
January 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28932114/spermidine-mediated-poly-lactic-co-glycolic-acid-nanoparticles-containing-fluorofenidone-for-the-treatment-of-idiopathic-pulmonary-fibrosis
#16
Jing Tang, Jianming Li, Guo Li, Haitao Zhang, Ling Wang, Dai Li, Jinsong Ding
Idiopathic pulmonary fibrosis is a progressive, fatal lung disease with poor survival. The advances made in deciphering this disease have led to the approval of different antifibrotic molecules, such as pirfenidone and nintedanib. An increasing number of studies with particles (liposomes, nanoparticles [NPs], microspheres, nanopolymersomes, and nanoliposomes) modified with different functional groups have demonstrated improvement in lung-targeted drug delivery. In the present study, we prepared, characterized, and evaluated spermidine (Spd)-modified poly(lactic- co -glycolic acid) (PLGA) NPs as carriers for fluorofenidone (AKF) to improve the antifibrotic efficacy of this drug in the lung...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28893276/imipramine-blocks-acute-silicosis-in-a-mouse-model
#17
Rupa Biswas, Kevin L Trout, Forrest Jessop, Jack R Harkema, Andrij Holian
BACKGROUND: Inhalation of crystalline silica is associated with pulmonary inflammation and silicosis. Although silicosis remains a prevalent health problem throughout the world, effective treatment choices are limited. Imipramine (IMP) is a FDA approved tricyclic antidepressant drug with lysosomotropic characteristics. The aim of this study was to evaluate the potential for IMP to reduce silicosis and block phagolysosome membrane permeabilization. METHODS: C57BL/6 alveolar macrophages (AM) exposed to crystalline silica ± IMP in vitro were assessed for IL-1β release, cytotoxicity, particle uptake, lysosomal stability, and acid sphingomyelinase activity...
September 11, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28890203/regional-aerosol-deposition-in-the-human-airways-the-siminhale-benchmark-case-and-a-critical-assessment-of-in-silico-methods
#18
P Koullapis, S C Kassinos, J Muela, C Perez-Segarra, J Rigola, O Lehmkuhl, Y Cui, M Sommerfeld, J Elcner, M Jicha, I Saveljic, N Filipovic, F Lizal, L Nicolaou
Regional deposition effects are important in the pulmonary delivery of drugs intended for the topical treatment of respiratory ailments. They also play a critical role in the systemic delivery of drugs with limited lung bioavailability. In recent years, significant improvements in the quality of pulmonary imaging have taken place, however the resolution of current imaging modalities remains inadequate for quantifying regional deposition. Computational Fluid-Particle Dynamics (CFPD) can fill this gap by providing detailed information about regional deposition in the extrathoracic and conducting airways...
February 15, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28851623/diethylcarbamazine-a-potential-treatment-drug-for-pulmonary-hypertension
#19
Edlene Lima Ribeiro, Ingrid Tavares Fragoso, Fabiana Oliveira Dos Santos Gomes, Amanda Costa Oliveira, Amanda Karoline Soares E Silva, Patrícia Martins E Silva, Bianca Torres Ciambarella, Isalira Peroba Rezende Ramos, Christina Alves Peixoto
The present study demonstrated the potential effects of diethylcarbamazine (DEC) on monocrotaline (MCT)-induced pulmonary hypertension. MCT solution (600mg/kg) was administered once per week, and 50mg/kg body weight of DEC for 28days. Three C57Bl/6 male mice groups (n=10) were studied: Control; MCT28, and MCT28 /DEC. Echocardiography analysis was performed and lung tissues were collected for light microscopy (hematoxylin-eosin and Masson's trichrome staining), immunohistochemistry (αSMA, FADD, caspase 8, caspase 3, BAX, BCL2, cytochrome C and caspase 9) western blot (FADD, caspase 8, caspase 3, BAX, BCL2, cytochrome C and caspase 9) and qRt-PCR (COL-1α and αSMA)...
October 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28836991/modeling-dna%C3%A2-damage-induced-pneumopathy-in-mice-insight-from-danger-signaling-cascades
#20
REVIEW
Florian Wirsdörfer, Verena Jendrossek
Radiation-induced pneumonitis and fibrosis represent severe and dose-limiting side effects in the radiotherapy of thorax-associated neoplasms leading to decreased quality of life or - as a consequence of treatment with suboptimal radiation doses - to fatal outcomes by local recurrence or metastatic disease. It is assumed that the initial radiation-induced damage to the resident cells triggers a multifaceted damage-signalling cascade in irradiated normal tissues including a multifactorial secretory program. The resulting pro-inflammatory and pro-angiogenic microenvironment triggers a cascade of events that can lead within weeks to a pronounced lung inflammation (pneumonitis) or after months to excessive deposition of extracellular matrix molecules and tissue scarring (pulmonary fibrosis)...
August 24, 2017: Radiation Oncology
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