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Lung drug deposition study

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https://www.readbyqxmd.com/read/28510480/dry-powder-inhaler-formulation-of-rifampicin-an-improved-targeted-delivery-system-for-alveolar-tuberculosis
#1
Tejal Rawal, Laurent Kremer, Iman Halloum, Shital Butani
BACKGROUND: The delivery of antitubercular drugs through direct lung targeting can lead to reduction in the dose as well as side effects of the drug. In the present investigation, carrier (lactose)-based dry-powder inhaler of rifampicin was prepared to achieve direct targeting of the drug into the lungs. METHODS: The dry powder inhaler formulation was prepared by simply mixing micronized rifampicin with coarse and fine lactose preblend. Preliminary blends of the drug were prepared with various lactose grades (Inhalac(®), Respitose,(®) and Lactohale(®))...
May 16, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/28507469/lungs-deposition-and-pharmacokinetic-study-of-submicron-budesonide-particles-in-wistar-rats-intended-for-immediate-effect-in-asthma
#2
Abdul Rauf, Aseem Bhatnagar, S S Sisodia, Roop K Khar, Farhan J Ahmad
The purpose of the present investigation was to study the aerosolization, lungs deposition and pharmacokinetic study of inhalable submicron particles of budesonide in male Wistar rats. Submicron particles were prepared by antisolvent nanoprecipitation method and freeze-dried to obtain free flowing powder. The freeze-drying process yielded dry powder with desirable aerodynamic properties for inhalation therapy. An in-house model inhaler was designed to deliver medicine to lungs, optimized at dose level of 10 mg for 30 sec of fluidization...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28504252/pulmonary-delivery-of-nanoparticle-chemotherapy-for-the-treatment-of-lung-cancers-challenges-and-opportunities
#3
REVIEW
Sharad Mangal, Wei Gao, Tonglei Li, Qi Tony Zhou
Lung cancer is the second most prevalent and the deadliest among all cancer types. Chemotherapy is recommended for lung cancers to control tumor growth and to prolong patient survival. Systemic chemotherapy typically has very limited efficacy as well as severe systemic adverse effects, which are often attributed to the distribution of anticancer drugs to non-targeted sites. In contrast, inhalation routes permit the delivery of drugs directly to the lungs providing high local concentrations that may enhance the anti-tumor effect while alleviating systemic adverse effects...
May 1, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28463044/aerosol-delivery-with-two-nebulizers-through-high-flow-nasal-cannula-a-randomized-cross-over-single-photon-emission-computed-tomography-computed-tomography-study
#4
Jonathan Dugernier, Michel Hesse, Thibaud Jumetz, Emilie Bialais, Jean Roeseler, Virginie Depoortere, Jean-Bernard Michotte, Xavier Wittebole, Stephan Ehrmann, Pierre-François Laterre, François Jamar, Gregory Reychler
BACKGROUND: High-flow nasal cannula use is developing in ICUs. The aim of this study was to compare aerosol efficiency by using two nebulizers through a high-flow nasal cannula: the most commonly used jet nebulizer (JN) and a more efficient vibrating-mesh nebulizer (VN). METHODS: Aerosol delivery of diethylenetriaminepentaacetic acid labeled with technetium-99m (4 mCi/4 mL) to the lungs by using a VN (Aerogen Solo(®); Aerogen Ltd., Galway, Ireland) and a constant-output JN (Opti-Mist Plus Nebulizer(®); ConvaTec, Bridgewater, NJ) through a high-flow nasal cannula (Optiflow(®); Fisher & Paykel, New Zealand) was compared in six healthy subjects...
May 2, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/28463041/effect-of-pressurized-metered-dose-inhaler-spray-characteristics-and-particle-size-distribution-on-drug-delivery-efficiency
#5
Morteza Yousefi, Kiao Inthavong, Jiyuan Tu
BACKGROUND: A key issue in pulmonary drug delivery is improvement of the delivery device for effective and targeted treatment. Pressurized metered dose inhalers (pMDIs) are the most popular aerosol therapy device for treating lung diseases. This article studies the effect of spray characteristics: injection velocity, spray cone angle, particle size distribution (PSD), and its mass median aerodynamic diameter (MMAD) on drug delivery. METHODS: An idealized oral airway geometry, extending from mouth to the main bronchus, was connected to a pMDI device...
May 2, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/28448027/dry-powder-and-nebulized-aerosol-inhalation-of-pharmaceuticals-delivered-to-mice-using-a-nose-only-exposure-system
#6
Jonathan E Phillips, Xuxia Zhang, James A Johnston
Obstructive respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD) are currently treated by inhaled anti-inflammatory and bronchodilator drugs. Despite the availability of multiple treatments, both diseases are growing public health concerns. The majority of asthma patients are well controlled on current inhaled therapies but a substantial number of patients with severe asthma are not. Asthma affects an estimated 300 million people worldwide and approximately 20 percent have a severe form of the disease...
April 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28424691/increased-autophagy-related-5-gene-expression-is-associated-with-collagen-expression-in-the-airways-of-refractory-asthmatics
#7
Audrey H Poon, David F Choy, Fazila Chouiali, Rakhee K Ramakrishnan, Bassam Mahboub, Severine Audusseau, Andrea Mogas, Jeffrey M Harris, Joseph R Arron, Catherine Laprise, Qutayba Hamid
BACKGROUND: Fibrosis, particularly excessive collagen deposition, presents a challenge for treating asthmatic individuals. At present, no drugs can remove or reduce excessive collagen in asthmatic airways. Hence, the identification of pathways involved in collagen deposition would help to generate therapeutic targets to interfere with the airway remodeling process. Autophagy, a cellular degradation process, has been shown to be dysregulated in various fibrotic diseases, and genetic association studies in independent human populations have identified autophagy-related 5 (ATG5) to be associated with asthma pathogenesis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28389274/significance-of-breath-hold-time-in-dry-powder-aerosol-drug-therapy-of-copd-patients
#8
Alpár Horváth, Imre Balásházy, Gábor Tomisa, Árpád Farkas
Aerosol drugs are effectively used to treat chronic respiratory diseases. The efficiency of the therapy depends also on the amount and distribution of drug deposited within the airways. The objective of this study is to apply numerical techniques to analyse the effect of the duration of breath-hold after the inhalation of six different commercialized dry powder drugs on their lung deposition. For this purpose a computational airway deposition model has been adapted and validated to the special case of therapeutic aerosols...
April 4, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28374433/clinical-implications-of-pseudomonas-aeruginosa-location-in-the-lungs-of-patients-with-cystic-fibrosis
#9
REVIEW
J E Moore, P Mastoridis
WHAT IS KNOWN AND OBJECTIVE: Pseudomonas aeruginosa is the leading cause of lung infection in patients with cystic fibrosis (CF) and is associated with significant morbidity and mortality. Antibiotics are regarded as the foundational pharmacological treatment for the suppressive management of chronic P. aeruginosa infections and to eradicate the first infection by P. aeruginosa. Inhalation remains a preferred route for drug administration, providing direct access to the site of infection while minimizing systemic side effects...
June 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28363192/rifampicin-loaded-chitosan-nanoparticle-dry-powder-presents-an-improved-therapeutic-approach-for-alveolar-tuberculosis
#10
Tejal Rawal, Rajesh Parmar, Rajeev K Tyagi, Shital Butani
Current treatment therapeutic approach for tuberculosis is the administration of first line drugs in the form of tablets and capsules for 4-6 months. However, this approach leads to severe adverse effects. Therefore, present study was designed to achieving local and sustained targeting of anti-tubercular drugs in order to reduce dose and frequency. The nanoparticle based dry powder formulation of rifampicin was developed and analyzed with respect to its direct targeting potential of lungs. Rifampicin loaded nanoparticles were formulated by ionic gelation probe sonication method, and characterized with respect to particle size, zeta potential, entrapment and drug loading efficiency...
June 1, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28357073/effect-of-bosentan-is-correlated-with-mmp-9-timp-1-ratio-in-bleomycin-induced-pulmonary-fibrosis
#11
Wan-Li Zuo, Jie-Min Zhao, Ji-Xiong Huang, Wei Zhou, Ze-Hong Lei, Yan-Ming Huang, Yan-Fen Huang, Hai-Gang Li
Pulmonary fibrosis (PF) is a life-threatening non-tumorous disease characterized by progressive fibrosis and worsening lung function. Various drugs, such as bleomycin, can contribute to lung injury and PF, with lung injury potentially occurring in 10% of bleomycin users. Bleomycin is the most commonly used drug in the establishment of an animal model of PF in rats. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) serve an important role in controlling tissue organization and fibrosis following injury...
February 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28332899/in-vitro-tests-for-aerosol-deposition-v-using-realistic-testing-to-estimate-variations-in-aerosol-properties-at-the-trachea
#12
Xiangyin Wei, Michael Hindle, Renishkumar R Delvadia, Peter R Byron
BACKGROUND: The dose and aerodynamic particle size distribution (APSD) of drug aerosols' exiting models of the mouth and throat (MT) during a realistic inhalation profile (IP) may be estimated in vitro and designated Total Lung Dose, TLDin vitro, and APSDTLDin vitro, respectively. These aerosol characteristics likely define the drug's regional distribution in the lung. METHODS: A general method was evaluated to enable the simultaneous determination of TLDin vitro and APSDTLDin vitro for budesonide aerosols' exiting small, medium and large VCU-MT models...
March 23, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
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
#13
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
#14
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
#15
Qi Liu, Jun-Xia Jiang, Ya-Nan Liu, Ling-Tian Ge, 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...
May 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28290122/scientific-rationale-for-determining-the-bioequivalence-of-inhaled-drugs
#16
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
#17
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)...
June 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28282259/study-on-the-pulmonary-delivery-system-of-apigenin-loaded-albumin-nanocarriers-with-antioxidant-activity
#18
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
#19
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
#20
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...
May 2017: Respiratory Care
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