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Lung drug deposition study

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https://www.readbyqxmd.com/read/28165252/cocktail-of-superoxide-dismutase-and-fasudil-encapsulated-in-targeted-liposomes-slows-pah-progression-at-a-reduced-dosing-frequency
#1
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...
February 17, 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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...
October 27, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27979017/inhalation-devices-delivery-systems-and-patient-technique
#12
Harold S Nelson
BACKGROUND: In real-life clinical settings, physicians often consider the properties of various inhaled corticosteroids (ICSs), but typically little consideration is given to the properties of different inhalers and formulations. OBJECTIVE: To discuss the effects of inhalation devices and user technique on efficacy, safety, and adherence with the aim of improving asthma management. METHODS: Relevant publications were selected to augment discussion...
December 2016: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/27977216/inhalation-of-respirable-crystalline-rifapentine-particles-induces-pulmonary-inflammation
#13
Thaigarajan Parumasivam, Anneliese S Ashhurst, Gayathri Nagalingam, Warwick J Britton, Hak-Kim Chan
Rifapentine is an anti-tuberculosis (anti-TB) drug with a prolonged half-life, but oral delivery results in low concentrations in the lungs because of its high binding (98%) to plasma proteins. We have shown that inhalation of crystalline rifapentine overcomes the limitations of oral delivery by significantly enhancing and prolonging the drug concentration in the lungs. The delivery of crystalline particles to the lungs may promote inflammation. This in vivo study characterizes the inflammatory response caused by pulmonary deposition of the rifapentine particles...
January 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27968887/infection-prevention-with-natural-protein-based-coating-on-the-surface-of-foley-catheters-a-randomised-controlled-clinical-trial
#14
Peng Zhao, Qijing Chen, Chao Lin, Zhaofen Lin, Liang Chang, Xiaoping Shao, Yueming Li, Jiangong Zhang, Zhongpeng Fan, Xuejun Wen
BACKGROUND: Health-care-associated infections characterised by antibiotic drug resistance are a global medical challenge that claims billions of dollars of health-care expenditure. Bacterial adhesion and subsequent formation of biofilms on catheters and tubes are the primary mechanisms through which these infections are initiated and propagated. We tested the efficacy and safety for clinical treatment of a coating based on natural protein, in which immunogenicity was eliminated through physical plasticising, applied to the surfaces of medical devices to inhibit bacterial adhesion...
October 2016: Lancet
https://www.readbyqxmd.com/read/27934123/aspects-of-quantitation-in-mass-spectrometry-imaging-investigated-on-cryo-sections-of-spiked-tissue-homogenates
#15
Heidi Toft Hansen, Christian Janfelt
Internal standards have been introduced in quantitative mass spectrometry imaging in order to compensate for differences in intensities throughout an image caused by, for example, difference in ion suppression or analyte extraction efficiency. To test how well the internal standards compensate for differences in tissue types in, for example, whole-body imaging, a set of tissue homogenates of different tissue types (lung, liver, kidney, heart, and brain) from rabbit was spiked to the same concentration with the drug amitriptyline and imaged in the same experiment using isotope labeled amitriptyline as internal standard...
December 6, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/27921442/nebulized-antibiotics-in-mechanically-ventilated-patients-roadmap-and-challenges
#16
G Poulakou, G Siakallis, S Tsiodras, A Arfaras-Melainis, G Dimopoulos
Nebulized antibiotics use has become common practice in the therapeutics of pneumonia in cystic fibrosis patients. There is an increasing interest in their use for respiratory infections in mechanically ventilated (MV) patients in order to a) overcome pharmacokinetic issues in the lung compartment with traditional systemic antibiotic use and b) prevent the emergence of multi-drug-resistant (MDR) pathogens. Areas covered: The beneficial effects of antibiotic nebulization in MV patients e.g. increasing efficacy, reduced toxicity and prevention of resistance are described...
January 2, 2017: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/27911474/is-chelation-therapy-efficient-for-the-treatment-of-intravenous-metallic-mercury-intoxication
#17
Daniela Pelclova, Stepanka Vlckova, Ondrej Bezdicek, Manuela Vaneckova, Pavel Urban, Petr Ridzon, Pavel Diblik, Tomas Navratil, Pavlina Klusackova, Kamil Vlcek, Olga Benesova, Pavel Trestik, Jiri Homolka, Sergey Zakharov
The efficacy of treatment for intravenous elemental mercury intoxication has not been fully studied with regard to clinical outcome, and treatment recommendations vary. We treated a 41-year-old man with a history of drug abuse and depression who attempted suicide using 1 mL (13.53 g) metallic Hg i.v. He was admitted to the hospital 2 months later for dyspnoea and thoracic pain and was diagnosed with pneumonia. Hg deposits were seen in the lungs and extra-pulmonary organs. His blood level (372 μg/L) exceeded the population level of 5 μg/L by more than 70 times...
December 2, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27853177/difference-in-resistance-to-humidity-between-commonly-used-dry-powder-inhalers-an-in-vitro-study
#18
Christer Janson, Thomas Lööf, Gunilla Telg, Georgios Stratelis, Folke Nilsson
Multi-dose dry powder inhalers (DPIs) are commonly used in asthma and chronic obstructive lung disease (COPD) treatment. A disadvantage is their sensitivity to humidity. In real life, DPIs are periodically exposed to humid conditions, which may affect aerosol characteristics and lung deposition. This study compared DPI aerosol performance after exposure to humidity. Budesonide (BUD) inhalers (Turbuhaler; Novolizer; Easyhaler) and budesonide/formoterol (BUD/FORM) inhalers (Turbuhaler; Spiromax; Easyhaler) were stored in 75% relative humidity (RH) at both ambient temperature and at -0 °C...
November 17, 2016: NPJ Primary Care Respiratory Medicine
https://www.readbyqxmd.com/read/27836120/computationally-efficient-analysis-of-particle-transport-and-deposition-in-a-human-whole-lung-airway-model-part-ii-dry-powder-inhaler-application
#19
Arun V Kolanjiyil, Clement Kleinstreuer, Ruxana T Sadikot
Pulmonary drug delivery is becoming a favored route for administering drugs to treat both lung and systemic diseases. Examples of lung diseases include asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD) as well as respiratory distress syndrome (ARDS) and pulmonary fibrosis. Special respiratory drugs are administered to the lungs, using an appropriate inhaler device. Next to the pressurized metered-dose inhaler (pMDI), the dry powder inhaler (DPI) is a frequently used device because of the good drug stability and a minimal need for patient coordination...
November 3, 2016: Computers in Biology and Medicine
https://www.readbyqxmd.com/read/27825470/monoclonal-igm-related-al-amyloidosis
#20
REVIEW
Paolo Milani, Giampaolo Merlini
Monoclonal immunoglobulin M (IgM)-related light chain (AL) amyloidosis, which accounts for 5%-7% of all AL amyloidosis cases, is a distinct clinical entity that poses specific challenges to clinicians. Several studies reported that although there is a substantial overlap, the pattern of organ involvement is peculiar, with higher frequencies of lung, lymph nodes, and peripheral nervous system involvement. A recent collaborative study from three European referral centers, defined that cardiac involvement, advanced Mayo disease stage, neuropathic, and liver involvement were independent factors that had impact on survival in IgM-AL amyloidosis patients...
June 2016: Best Practice & Research. Clinical Haematology
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