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Pulmonary Drug deposition models

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https://www.readbyqxmd.com/read/29079338/advances-in-experimental-and-mechanistic-computational-models-to-understand-pulmonary-exposure-to-inhaled-drugs
#1
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...
October 25, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29058607/aerosol-delivery-during-invasive-mechanical-ventilation-a-systematic-review
#2
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
#3
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
#4
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
#5
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...
September 20, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28940894/the-antiretroviral-nelfinavir-mesylate-a-potential-therapy-for-systemic-scleroderma
#6
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
#7
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
#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/28851623/diethylcarbamazine-a-potential-treatment-drug-for-pulmonary-hypertension
#10
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
#11
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/28809501/microencapsulated-solid-lipid-nanoparticles-as-a-hybrid-platform-for-pulmonary-antibiotic-delivery
#12
Diana P Gaspar, Maria Manuela Gaspar, Carla V Eleutério, Ana Grenha, Mateo Blanco, Lídia M D Gonçalves, Pablo Taboada, António J Almeida, Carmen Remuñán-López
Solid lipid nanoparticles (SLN) containing rifabutin (RFB), with pulmonary administration purposes, were developed through a technique that avoids the use of organic solvents or sonication. To facilitate their pulmonary delivery, the RFB-loaded SLN were included in microspheres of appropriate size using suitable excipients (mannitol and trehalose) through a spray-drying technique. Confocal analysis microscopy showed that microspheres are spherical and that SLN are efficiently microencapsulated and homogeneously distributed throughout the microsphere matrices...
August 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28809447/pulmonary-delivery-of-tea-tree-oil-%C3%AE-cyclodextrin-inclusion-complexes-for-the-treatment-of-fungal-and-bacterial-pneumonia
#13
Miao Li, Lifei Zhu, Tongtong Zhang, Boming Liu, Lina Du, Yiguang Jin
OBJECTIVES: Bacterial pneumonia is a common cause of death worldwide. Tea tree oil (TTO) is a potent antimicrobial natural product, which is formulated in dry powder inhalers (DPIs) for the treatment of fungal and bacterial pneumonia. METHODS: Tea tree oil-β-cyclodextrin inclusion complexes (TTO-β-CD) were prepared and characterized. Aerodynamic properties of TTO-β-CD powders were measured. The rat models of fungal (Candida albicans) and bacterial (Acinetobacter baumannii) pneumonia were prepared...
August 15, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28783251/safety-and-efficacy-of-allogeneic-lung-spheroid-cells-in-a-mismatched-rat-model-of-pulmonary-fibrosis
#14
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
#15
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/28774811/the-interaction-of-dendrimer-doxorubicin-conjugates-with-a-model-pulmonary-epithelium-and-their-cosolvent-free-pseudo-solution-formulations-in-pressurized-metered-dose-inhalers
#16
Qian Zhong, Bruno V Humia, Alisha R Punjabi, Francine F Padilha, Sandro R P da Rocha
Oral inhalation (OI) of nano-chemotherapeutics holds great potentials in the treatment of lung cancers as it enables direct targeting of drugs to lung tissues, spatial and temporal control of drug release, and decrease in drug-associated systemic and local lung toxicity. Therefore, the design of chemistry of the nanocarriers and their OI formulations for chemotherapeutics delivery to the peripheral lungs and extrapulmonary tissues of relevance such as lymph nodes, may thus afford new opportunities for treating such relevant diseases...
July 31, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28720675/the-effect-of-nebulizer-position-on-aerosolized-epoprostenol-delivery-in-an-adult-lung-model
#17
Allison C Anderson, Meagan N Dubosky, Kelly A Fiorino, Vanessa Quintana, Carl A Kaplan, David L Vines
BACKGROUND: Aerosolized epoprostenol is an alternative for inhaled nitric oxide in the management of pulmonary arterial hypertension and possibly acute hypoxemia. Our objective was to determine differences in drug deposition based on different nebulizer positions in the ventilator circuit, using a vibrating mesh nebulizer. METHODS: An 8.0-mm inner diameter endotracheal tube (ETT) was connected to a training test lung, compliance of 30 mL/cm H2O, with a collecting filter placed at the ETT-test lung junction...
November 2017: Respiratory Care
https://www.readbyqxmd.com/read/28684908/%C3%AE-bisabolol-loaded-lipid-core-nanocapsules-reduce-lipopolysaccharide-induced-pulmonary-inflammation-in-mice
#18
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/28684363/investigation-of-multiphase-multicomponent-aerosol-flow-dictating-pmdi-spacer-interactions
#19
Saurabh Sarkar, S Prasad Peri, Bodhisattwa Chaudhuri
The use of Pressurized metered dose inhalers (pMDIs) for the treatment of asthma and other chronic obstructive pulmonary diseases is frequently associated with breath-actuation synchronization problems and poor pulmonary delivery, particularly amongst the pediatric and geriatric population groups. Spacers, or Valved Holding Chambers (VHCs), are frequently used to address these problems. However, the performance of spacers with different pMDIs is also highly variable and needs to be investigated. The purpose of the current study is to develop a computational fluid dynamics (CFD) model which can characterize multiphase multicomponent aerosol flow issuing from a commercial suspension-based pMDI into a spacer...
July 4, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28683222/application-of-a-one-dimensional-computational-model-for-the-prediction-of-deposition-from-a-dry-powder-inhaler
#20
Konstantinos Gourgoulianis, Zoi Daniil, Katerina Athanasiou, Stavroula Rozou, Vasileios Bontozoglou
BACKGROUND: Accurate prediction of the regional deposition of inhaled dry powders as a function of powder properties and breathing pattern is a long-term research goal for pulmonary drug delivery. In the present work, deposition along the respiratory tract of dry powders of Fluticasone propionate and Salmeterol is predicted. METHODS: A one-dimensional particle transport and deposition model is used, whose novelty is in the treatment of the alveolar space of each airway generation as an efficient mixing chamber...
July 6, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
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