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Lung drug deposition study

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https://www.readbyqxmd.com/read/28322599/dissolvit-an-in-vitro-method-for-simulating-the-dissolution-and-absorption-of-inhaled-dry-powder-drugs-in-the-lungs
#1
Per Gerde, Maria Malmlöf, Lina Havsborn, Carl-Olof Sjöberg, Pär Ewing, Stefan Eirefelt, Katarina Ekelund
The main purpose of this work was to develop an in vitro method for simulating the dissolution and absorption of inhaled dry powder drugs that also mimics systemic pharmacokinetic data. A second purpose was to evaluate this method. DissolvIt(®) was developed as a simulation of the air-blood barrier of the upper airways, constituting: "airborne" particles deposited on a glass cover slip, a mucus simulant, a polycarbonate (basal) membrane, and a pumped albumin buffer simulating the pulmonary blood flow. The PreciseInhale(®) exposure system was used to aerosolize and deposit test formulations onto cover slips...
February 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28314802/an-ex-vivo-model-to-induce-early-fibrosis-like-changes-in-human-precision-cut-lung-slices
#2
Hani N Alsafadi, Claudia A Staab-Weijnitz, Mareike Lehmann, Michael Lindner, Britta Peschel, Melanie Königshoff, Darcy Elizabeth Wagner
IPF is a devastating chronic interstitial lung disease (ILD) characterized by lung tissue scarring and high morbidity. Lung epithelial injury, myofibroblast activation, and deranged repair are believed to be key processes involved in disease onset and progression but the exact molecular mechanisms behind IPF remain unclear. Several drugs have been shown to slow disease progression, but treatments which halt or reverse IPF progression have not been identified. Ex vivo models of human lung have been proposed for drug discovery, one of which is precision-cut lung slices (PCLS)...
March 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28300665/grape-seed-extract-ameliorates-bleomycin-induced-mouse-pulmonary-fibrosis
#3
Qi Liu, Jun-Xia Jiang, Ya-Nan Liu, Yan Guan, Wei Zhao, Yong-Liang Jia, Xin-Wei Dong, Yun Sun, Qiang-Min Xie
Pulmonary fibrosis is common in a variety of inflammatory lung diseases, such as interstitial pneumonia, chronic obstructive pulmonary disease, and silicosis. There is currently no effective clinical drug treatment. It has been reported that grape seed extracts (GSE) has extensive pharmacological effects with minimal toxicity. Although it has been found that GSE can improve the lung collagen deposition and fibrosis pathology induced by bleomycin in rat, its effects on pulmonary function, inflammation, growth factors, matrix metalloproteinases and epithelial-mesenchymal transition remain to be researched...
March 11, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28290122/scientific-rationale-for-determining-the-bioequivalence-of-inhaled-drugs
#4
REVIEW
Omar S Usmani, Mathieu Molimard, Vaibhav Gaur, Jaideep Gogtay, Gur Jai Pal Singh, Geena Malhotra, Eric Derom
In recent years, pathways for the development and approval of bioequivalent inhaled products have been established for regulated markets, including the European Union (EU), and a number of orally inhaled products (OIPs) have been approved in the EU solely on the basis of in vitro and pharmacokinetic data. This review describes how these development pathways are structured and their implications for the treatment of airway diseases such as asthma. The EU guidance follows a stepwise approach that includes in vitro criteria as the first step...
March 13, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28289922/curcumin-inhibits-lipopolysaccharide-lps-induced-endotoxemia-and-airway-inflammation-through-modulation-of-sequential-release-of-inflammatory-mediators-tnf-%C3%AE-and-tgf-%C3%AE-1-in-murine-model
#5
Asha Kumari, D Dash, Rashmi Singh
OBJECTIVE: Curcumin (diferuloylmethane), a major component of turmeric is well known for its anti-inflammatory potential. Present study investigates sequential release of inflammatory mediators post LPS challenge (10 mg/kg,i.p.) causing lung inflammation and its modulation by curcumin through different routes (20 mg/kg, i.p and 10 mg/kg, i.n.) in murine model. Dexamethasone (1 mg/kg, i.p) was used as standard drug. METHODS: Lung Inflammation was evaluated by histopathological analysis, myeloperoxidase (MPO) activity followed by inflammatory cell count and total protein content measurements in bronchoalveolar fluid (BALF)...
March 13, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28282259/study-on-the-pulmonary-delivery-system-of-apigenin-loaded-albumin-nanocarriers-with-antioxidant-activity
#6
Zsófia Edit Pápay, Annamária Kósa, Béla Böddi, Zahra Merchant, Imran Y Saleem, Mohammed Gulrez Zariwala, Imre Klebovich, Satyanarayana Somavarapu, István Antal
BACKGROUND: Respiratory diseases are mainly derived from acute and chronic inflammation of the alveoli and bronchi. The pathophysiological mechanisms of pulmonary inflammation mainly arise from oxidative damage that could ultimately lead to acute lung injury. Apigenin (Api) is a natural polyphenol with prominent antioxidant and anti-inflammatory properties in the lung. Inhalable formulations that consist of nanoparticles (NPs) have several advantages over other administration routes, and therefore, this study investigated the application of apigenin-loaded bovine serum albumin nanoparticles (BSA-Api-NPs) for pulmonary delivery...
March 10, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/28276786/pulmonary-delivery-systems-for-polyphenols
#7
Valentina Trotta, Santo Scalia
This review reports on the beneficial pharmacological properties of naturally occurring polyphenols for the treatment of inflammatory pulmonary diseases. In addition, it presents an overview of the different types of inhalable formulations which have been developed in order to achieve efficient delivery of polyphenols to the respiratory tract. The main biological activities of polyphenols (anti-oxidant and anti-inflammatory) are covered, with particular emphasis on the studies describing their therapeutic effects on different factors and conditions characteristic of lung pathologies...
February 28, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28270542/effects-of-heat-and-moisture-exchangers-and-exhaled-humidity-on-aerosol-deposition-in-a-simulated-ventilator-dependent-adult-lung-model
#8
Arzu Ari, Khalid S Alwadeai, James B Fink
BACKGROUND: Many in vitro models report higher inhaled dose with dry versus heated humidity. Heat-and-moisture exchangers (HMEs) provide passive humidity in ventilator-dependent patients but act as a barrier to aerosol. The HMEs designed to allow aerosol delivery (HME-ADs) have not been well described. The purpose of this study is to determine the impact on aerosol deposition of HME-ADs with and without active exhaled humidity in a simulated ventilator-dependent adult model. METHODS: We used an in vitro lung model consisting of an intubated teaching mannequin with an endotracheal tube of 8...
March 7, 2017: Respiratory Care
https://www.readbyqxmd.com/read/28257580/a-novel-antifibrotic-mechanism-of-nintedanib-and-pirfenidone-inhibition-of-collagen-fibril-assembly
#9
Larissa Knüppel, Yoshihiro Ishikawa, Michaela Aichler, Katharina Heinzelmann, Rudolf Hatz, Jürgen Behr, Axel Walch, Hans Peter Bächinger, Oliver Eickelberg, Claudia A Staab-Weijnitz
RATIONALE: Idiopathic pulmonary fibrosis (IPF) is characterized by excessive deposition of extracellular matrix, in particular collagens. Two IPF therapeutics, nintedanib and pirfenidone, decelerate lung function decline, but their underlying mechanisms of action are poorly understood. In this study we sought to analyze their effects on collagen synthesis and maturation at important regulatory levels. METHODS: Primary human fibroblasts from IPF patients and healthy donors were treated with nintedanib (0...
March 3, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28165252/cocktail-of-superoxide-dismutase-and-fasudil-encapsulated-in-targeted-liposomes-slows-pah-progression-at-a-reduced-dosing-frequency
#10
Nilesh Gupta, Jahidur Rashid, Eva Nozik-Grayck, Ivan F McMurtry, Kurt R Stenmark, Fakhrul Ahsan
Currently, two or more pulmonary vasodilators are used to treat pulmonary arterial hypertension (PAH), but conventional vasodilators alone cannot reverse disease progression. In this study, we tested the hypothesis that a combination therapy comprising a vasodilator plus a therapeutic agent that slows pulmonary arterial remodeling and right heart hypertrophy is an efficacious alternative to current vasodilator-based PAH therapy. Thus, we encapsulated a cocktail of superoxide dismutase (SOD), a superoxide scavenger, and fasudil, a specific rho-kinase inhibitor, into a liposomal formulation equipped with a homing peptide, CAR...
March 6, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28161667/aerodynamic-properties-and-in-silico-deposition-of-meloxicam-potassium-incorporated-in-a-carrier-free-dpi-pulmonary-system
#11
Anita Chvatal, Árpád Farkas, Imre Balásházy, Piroska Szabó-Révész, Rita Ambrus
Dry powder inhalers (DPIs) have been among the fastest developing inhaler forms in the past decades. Researches are focusing on the formulation of carrier-free powders to obtain a higher deep-lung deposition and hereby to increase the effectiveness of the medicine. The aim of our study was to prepare a carrier-free dry powder formulation of meloxicam potassium (MP), a novel salt form of meloxicam, using a one-step co-spray drying technology. Different types of excipients were used to modify the crystal structure and to increase aerosolization efficacy...
February 1, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28161666/cellular-internalization-and-transport-of-biodegradable-polyester-dendrimers-on-a-model-of-the-pulmonary-epithelium-and-their-formulation-in-pressurized-metered-dose-inhalers
#12
Rodrigo S Heyder, Qian Zhong, Reinaldo C Bazito, Sandro R P da Rocha
The purpose of this study was to evaluate the effect of generation and surface PEGylation of degradable polyester-based dendrimers nanocarriers on their interactions with an in vitro model of the pulmonary epithelium as well as to assess the ability to formulate such carriers in propellant-based, portable oral-inhalation devices to determine their potential for local and systemic delivery of drugs to and through the lungs. Hydroxyl (-OH) terminated polyester dendrimers of generation 3 and 4 (G3, and G4) were synthesized using a divergent approach...
February 1, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28115845/long-term-intravenous-administration-of-carboxylated-single-walled-carbon-nanotubes-induces-persistent-accumulation-in-the-lungs-and-pulmonary-fibrosis-via-the-nuclear-factor-kappa-b-pathway
#13
Yue Qin, Suning Li, Gan Zhao, Xuanhao Fu, Xueping Xie, Yiyi Huang, Xiaojing Cheng, Jinbin Wei, Huagang Liu, Zefeng Lai
Numerous studies have demonstrated promising application of single-walled carbon nanotubes (SWNTs) in drug delivery, diagnosis, and targeted therapy. However, the adverse health effects resulting from intravenous injection of SWNTs are not completely understood. Studies have shown that levels of "pristine" or carboxylated carbon nanotubes are very high in mouse lungs after intravenous injection. We hypothesized that long-term and repeated intravenous administration of carboxylated SWNTs (c-SWNTs) can result in persistent accumulation and induce histopathologic changes in rat lungs...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28109773/exploring-polyvinylpyrrolidone-in-the-engineering-of-large-porous-plga-microparticles-via-single-emulsion-method-with-tunable-sustained-release-in-the-lung-in-vitro-and-in-vivo-characterization
#14
Rui Ni, Uwe Muenster, Jing Zhao, Lan Zhang, Eva-Maria Becker-Pelster, Martin Rosenbruch, Shirui Mao
Sustained pulmonary drug delivery is regarded as an effective strategy for local treatment of chronic lung diseases. Despite of the progress made so far, there remains a need for respirable drug loaded porous microparticles, where porosity of the microparticles can be readily engineered during the preparation process, with tunable sustained drug release upon lung deposition. In this work, polyvinyl pyrrolidone (PVP) was used as a novel porogen to engineer PLGA-based large porous particles (LPPs) using single emulsion method, with fine tuning of the porosity, sustained drug release both in vitro and in vivo...
January 18, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28075194/aerosol-drug-delivery-during-noninvasive-positive-pressure-ventilation-effects-of-intersubject-variability-and-excipient-enhanced-growth
#15
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
#16
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
#17
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...
February 2017: Respiratory Care
https://www.readbyqxmd.com/read/27993478/pharmaceutical-aerosols-deposition-patterns-from-a-dry-powder-inhaler-euler-lagrangian-prediction-and-validation
#18
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
#19
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
#20
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...
January 1, 2017: European Journal of Pharmaceutical Sciences
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