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Lung drug deposition study

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https://www.readbyqxmd.com/read/29453801/regional-deposition-of-nasal-sprays-in-adults-a-wide-ranging-computational-study
#1
Milad Kiaee, Herbert Wachtel, Michelle L Noga, Andrew R Martin, Warren H Finlay
The present work examines regional deposition within the nose for nasal sprays over a large and wide ranging parameter space by using numerical simulation. A set of seven realistic adult nasal airway geometries was defined based on Computed Tomography (CT) images. Deposition in six regions of each nasal airway geometry (the vestibule, valve, anterior turbinate, posterior turbinate, olfactory, and nasopharynx) was determined for varying particle diameter, spray cone angle, spray release direction, particle injection speed, and particle injection location...
February 17, 2018: International Journal for Numerical Methods in Biomedical Engineering
https://www.readbyqxmd.com/read/29409488/the-topical-study-of-inhaled-drug-salbutamol-delivery-in-idiopathic-pulmonary-fibrosis
#2
Omar S Usmani, Martyn F Biddiscombe, Shuying Yang, Sally Meah, Eunice Oballa, Juliet K Simpson, William A Fahy, Richard P Marshall, Pauline T Lukey, Toby M Maher
BACKGROUND: Our aim was to investigate total and regional lung delivery of salbutamol in subjects with idiopathic pulmonary fibrosis (IPF). METHODS: The TOPICAL study was a 4-period, partially-randomised, controlled, crossover study to investigate four aerosolised approaches in IPF subjects. Nine subjects were randomised to receive 99mTechnetium-labelled monodisperse salbutamol (1.5 μm or 6 μm; periods 1 and 2). Subjects also received radio-labelled salbutamol using a polydisperse nebuliser (period 3) and unlabelled salbutamol (400 μg) using a polydisperse pressurized metered dose inhaler with volumatic spacer (pMDI; period 4)...
February 6, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29297393/substance-deposition-assessment-in-obstructed-pulmonary-system-through-numerical-characterization-of-airflow-and-inhaled-particles-attributes
#3
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
#4
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/29180863/paclitaxel-and-quercetin-nanoparticles-co-loaded-in-microspheres-to-prolong-retention-time-for-pulmonary-drug-delivery
#5
Kang Liu, Weijuan Chen, Tingting Yang, Baofang Wen, Dejun Ding, Michael Keidar, Jinbao Tang, Weifen Zhang
High drug resistance, poor water solubility, short half-life, and low local drug concentration are obstacles for successful delivery of chemotherapeutic drugs for lung cancer. A new method involving the use of nanoparticles (NPs) for pulmonary delivery is proposed. However, use of NPs is limited by the particle size range for pulmonary drug delivery considering that NPs cannot be deposited directly into the lungs. NPs polymerized into microspheres (polymeric microspheres, PMs) will result in suitable particle sizes and retain the advantages of nanodrugs after redispersion when applied in pulmonary delivery...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29163164/lassbio-897-reduces-lung-injury-induced-by-silica-particles-in-mice-potential-interaction-with-the-a2a-receptor
#6
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/29150967/drug-delivery-strategies-for-chemoprevention-of-uvb-induced-skin-cancer-a-review
#7
REVIEW
Arvind Bagde, Arindam Mondal, Mandip Singh
Annually, more skin cancer cases are diagnosed than the collective incidence of the colon, lung, breast, and prostate cancer. Persistent contact with sunlight is a primary cause for all the skin malignancies. UVB radiation induces reactive oxygen species (ROS) production in the skin which eventually leads to DNA damage and mutation. Various delivery approaches for the skin cancer treatment/prevention have been evolving and are directed toward improvements in terms of delivery modes, therapeutic agents, and site-specificity of therapeutics delivery...
January 2018: Photodermatology, Photoimmunology & Photomedicine
https://www.readbyqxmd.com/read/29115860/lysyl-oxidase-like-1-protein-deficiency-protects-mice-from-adtgf-%C3%AE-1-induced-pulmonary-fibrosis
#8
Pierre-Simon Bellaye, Chiko Shimbori, Chandak Upagupta, Seidai Sato, Wei Shi, Jack Gauldie, Kjetil Ask, Martin Kolb
Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterised by excessive deposition of extracellular matrix (ECM) in the lung parenchyma. The abnormal ECM deposition slowly overtakes normal lung tissue disturbing gas-exchange and leading to respiratory failure and death. ECM cross-linking and subsequent stiffening is thought to be a major contributor of disease progression and also promotes the activation of TGF-β1, one of the main pro-fibrotic growth factors. Lysyl oxidase-like1 (LOXL1) belongs to the crosslinking enzyme family and has been shown to be upregulated in active fibrotic regions of bleomycin-treated mice and IPF patients...
November 8, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29058607/aerosol-delivery-during-invasive-mechanical-ventilation-a-systematic-review
#9
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/29054517/size-distribution-of-salbutamol-ipratropium-aerosols-produced-by-different-nebulizers-in-the-absence-and-presence-of-heat-and-humidification
#10
Ssu-Han Yang, Tsung-Ming Yang, Hui-Ling Lin, Ying-Huang Tsai, Tien-Pei Fang, Gwo-Hwa Wan
BACKGROUND: Few studies have evaluated the size distribution of inhaled and exhaled aerosolized drugs, or the effect of heated humidification on particle size and lung deposition. The present study evaluated these aspects of bronchodilator (salbutamol/ipratropium) delivery using a lung model in the absence and presence of heat and humidification. METHODS: We positioned filters to collect and measure the initial drug, inhaled drug, and exhaled drug. Particle size distribution was evaluated using an 8-stage Marple personal cascade impactor with 0...
October 17, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29054499/coupled-in-silico-platform-computational-fluid-dynamics-cfd-and-physiologically-based-pharmacokinetic-pbpk-modelling
#11
Aleksandra Vulović, Tijana Šušteršič, Sandra Cvijić, Svetlana Ibrić, Nenad Filipović
One of the critical components of the respiratory drug delivery is the manner in which the inhaled aerosol is deposited in respiratory tract compartments. Depending on formulation properties, device characteristics and breathing pattern, only a certain fraction of the dose will reach the target site in the lungs, while the rest of the drug will deposit in the inhalation device or in the mouth-throat region. The aim of this study was to link the Computational fluid dynamics (CFD) with physiologically-based pharmacokinetic (PBPK) modelling in order to predict aerolisolization of different dry powder formulations, and estimate concomitant in vivo deposition and absorption of amiloride hydrochloride...
October 17, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29031615/the-leukotriene-receptor-antagonist-pranlukast-attenuates-airway-remodeling-by-suppressing-tgf-%C3%AE-signaling
#12
Jung Hur, Ji Young Kang, Chin Kook Rhee, Young Kyoon Kim, Sook Young Lee
BACKGROUND/OBJECTIVE: Asthma is a chronic airway disease characterized by airway eosinophilic inflammation and remodeling, which are associated with a loss in lung function. Although both contribute significantly to asthma pathogenesis, mechanistic studies and drug discovery have focused on inflammatory targets. In this study, we investigated the effect of the leukotriene receptor antagonist pranlukast on allergic airway inflammation and remodeling in vivo and in vitro. METHOD: Four groups of female BALB/c mice (control; ovalbumin [OVA]-sensitized and -challenged; dimethyl sulfoxide [DMSO]-treated OVA; and pranlukast-treated OVA) were examined...
October 12, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28941830/experimental-and-computational-study-of-the-effect-of-breath-actuated-mechanism-built-in-the-nexthaler-%C3%A2-dry-powder-inhaler
#13
Árpád Farkas, David Lewis, Tanya Church, Alan Tweedie, Francesca Mason, Allen E Haddrell, Jonathan P Reid, Alpár Horváth, Imre Balásházy
The breath-actuated mechanism (BAM) is a mechanical unit included in NEXThaler(®) with the role of delaying the emission of the drug until the inhalation flow rate of the patient is sufficiently high to detach the drug particles from their carriers. The main objective of this work was to analyse the effect of the presence of BAM on the size distribution of the emitted drug and its airway deposition efficiency and distribution. Study of the hygroscopic growth of the emitted drug particles and its effect on the deposition was another goal of this study...
November 25, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28940894/the-antiretroviral-nelfinavir-mesylate-a-potential-therapy-for-systemic-scleroderma
#14
Cecilia G Sanchez, Steven V Molinski, Rafael Gongora, Meredith Sosulski, Taylor Fuselier, Stephen S MacKinnon, Debasis Mondal, Joseph A Lasky
Transforming growth factor (TGF)-β1 is considered a key factor in fibrogenesis, and blocking TGF-β1 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 can be repurposed to treat pulmonary fibrosis in systemic scleroderma (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 (FMD) mediated by TGF-β1...
September 21, 2017: 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
#15
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/28923239/a-novel-formulation-of-inhaled-sodium-cromoglicate-pa101-in-idiopathic-pulmonary-fibrosis-and-chronic-cough-a-randomised-double-blind-proof-of-concept-phase-2-trial
#16
Surinder S Birring, Marlies S Wijsenbeek, Sanjay Agrawal, Jan W K van den Berg, Helen Stone, Toby M Maher, Ahmet Tutuncu, Alyn H Morice
BACKGROUND: Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied...
October 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28918665/considerations-in-establishing-bioequivalence-of-inhaled-compounds
#17
Irvin Mayers, Mohit Bhutani
Generic inhalers are often perceived as inferior to their branded counterparts; however, they are safe and effective if they can meet the regulatory requirements. The approach to assess bioequivalence (BE) in oral dosage form products is not sufficient to address the complexities of inhalational products (e.g., patient-device interface); hence, more considerations are needed and caution should be applied in determining BE of inhaled compounds. Areas covered: This review outlines the evaluation process for generic inhalers, explores the regulatory approaches in BE assessment, and highlights the considerations and challenges in the current in vitro and in vivo approaches (lung deposition, pharmacokinetic, pharmacodynamic/clinical studies, and patient-device interface) for establishing BE of inhaled compounds...
September 21, 2017: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/28903066/development-of-fine-solid-crystal-suspension-with-enhanced-solubility-stability-and-aerosolization-performance-for-dry-powder-inhalation
#18
Ling Lin, Guilan Quan, Tingting Peng, Zhengwei Huang, Vikramjeet Singh, Ming Lu, Chuanbin Wu
Dry powder for inhalation (DPI) is an attractive approach for the treatment of local lung diseases. However, the application of drugs with poor water solubility is often limited due to the dissolution obstacles in the fluid layer of the lung lining. In this study, fine solid-crystal suspension (FSCS) was proposed as a solvent-free method to improve the solubility of a drug with poor solubility (itraconazole) and achieve high deposition efficiency simultaneously. The FSCS, in which the crystalline drug particle was highly dispersed in the crystalline excipient, was initially prepared as drug-excipient extrudate by hot melt extrusion, followed by jet milling into fine particles...
November 25, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28893276/imipramine-blocks-acute-silicosis-in-a-mouse-model
#19
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
#20
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...
September 7, 2017: European Journal of Pharmaceutical Sciences
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