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Lung drug deposition study

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https://www.readbyqxmd.com/read/29031615/the-leukotriene-receptor-antagonist-pranlukast-attenuates-airway-remodeling-by-suppressing-tgf-%C3%AE-signaling
#1
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
#2
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...
September 21, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28940894/the-antiretroviral-nelfinavir-mesylate-a-potential-therapy-for-systemic-scleroderma
#3
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
#4
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
#5
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
#6
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
#7
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...
September 10, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28893276/imipramine-blocks-acute-silicosis-in-a-mouse-model
#8
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
#9
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
https://www.readbyqxmd.com/read/28882385/lung-deposition-and-systemic-bioavailability-of-different-aerosol-devices-with-and-without-humidification-in-mechanically-ventilated-patients
#10
Islam O F Moustafa, Mohammed R A-A Ali, Moataz Al Hallag, Hoda Rabea, James B Fink, Patricia Dailey, Mohamed E A Abdelrahim
BACKGROUND: During mechanical ventilation medical aerosol delivery has been reported to be upto two fold greater with dry inhaled gas than with heated humidity. Urine levels at 0.5 h post dose (URSAL0.5%) has been confirmed as an index of lung deposition and 24 h (URSAL24%) as index of systemic absorption. Our aim was to determine the effect of humidification and aerosol device type on drug delivery to ventilated patients using urine levels. METHODS: In a randomized crossover design, 36 (18female) mechanically ventilated patients were assigned to one of three groups...
September 4, 2017: Heart & Lung: the Journal of Critical Care
https://www.readbyqxmd.com/read/28880765/the-development-and-validation-of-an-in-vitro-airway-model-to-assess-realistic-airway-deposition-and-drug-permeation-behavior-of-orally-inhaled-products-across-synthetic-membranes
#11
Bao K Huynh, Daniela Traini, Dale R Farkas, P Worth Longest, Michael Hindle, Paul M Young
BACKGROUND: Current in vitro approaches to assess lung deposition, dissolution, and cellular transport behavior of orally inhaled products (OIPs) have relied on compendial impactors to collect drug particles that are likely to deposit in the airway; however, the main drawback with this approach is that these impactors do not reflect the airway and may not necessarily represent drug deposition behavior in vivo. The aim of this article is to describe the development and method validation of a novel hybrid in vitro approach to assess drug deposition and permeation behavior in a more representative airway model...
September 7, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/28868971/mucoadhesive-solid-lipid-microparticles-for-controlled-release-of-a-corticosteroid-in-the-chronic-obstructive-pulmonary-disease-treatment
#12
Erika Amore, Maria Ferraro, Maria Letizia Manca, Mark Gjomarkaj, Gaetano Giammona, Elisabetta Pace, Maria Luisa Bondì
AIM: Therapeutic efficacy of pulmonary diseases is often limited and drug delivery systems offer new solutions to clinical problems. Solid lipid microparticles (SLMs) are suggested as systems for the delivery of therapeutics to the lung as, because of their size, they are able to deposit into secondary bronchi. MATERIALS & METHODS: Here, we describe two novel different SLMs using chitosan and alginate such as mucoadhesive polymers and we also studied their biocompatibility and their effectiveness compared with the free drug in controlling senescence and inflammatory processes in cigarette smoke extracts...
September 4, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28851623/diethylcarbamazine-a-potential-treatment-drug-for-pulmonary-hypertension
#13
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
#14
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
https://www.readbyqxmd.com/read/28829202/effect-of-heat-moisture-exchanger-on-aerosol-drug-delivery-and-airway-resistance-in-simulated-ventilator-dependent-adults-using-jet-and-mesh-nebulizers
#15
Arzu Ari, Truong Dang, Fahad H Al Enazi, Mohammed M Alqahtani, Abdulrahman Alkhathami, Rowaida Qoutah, Ahmad S Almamary, James B Fink
BACKGROUND: Placement of a heat moisture exchanger (HME) between aerosol generator and patient has been associated with greatly reduced drug delivery. The purpose of this study was to evaluate the effect of filtered and nonfiltered HMEs placed between nebulizer and patient on aerosol deposition and airway resistance (Raw) in simulated ventilator-dependent adults. METHODS: An in vitro lung model was developed to simulate a mechanically ventilated adult (Vt 500 mL, RR 15/min, and PEEP 5 cmH2O, using two inspiratory flow rates 40 and 50 L/min) using an intubated adult manikin with an endotracheal tube (8 mmID)...
August 22, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
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
#16
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
#17
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
#18
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
#19
REVIEW
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...
September 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%C3%A2-vivo
#20
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
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