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Lung drug deposition study

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https://www.readbyqxmd.com/read/29649591/inhalable-gadofullerenol-70-fullerenol-as-high-efficiency-ros-scavengers-for-pulmonary-fibrosis-therapy
#1
Yue Zhou, Mingming Zhen, Haijun Ma, Jie Li, Chunying Shu, Chunru Wang
Pulmonary fibrosis has become a fatal disease for its high incidence and few effective drugs available in clinic. In this study, gadofullerenol (GF-OH) and [70] fullerenol (C70 -OH) nanoparticles (NPs) prepared by a one-pot reaction were designed as nanomedicines to treat this fatal disease. It was revealed that the inhalation of gadofullerenols and [70] fullerenols substantially alleviates the collagen deposition induced by acute lung injury. Based on detailed studies of oxidative stress parameters and transforming growth factor-β1 (TGF-β1 ), we demonstrated they owned the antioxidant and anti-inflammatory functions for the modulation of ROS-mediated inflammation process...
April 9, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29623041/an-adaptogen-withaferin-a-ameliorates-in-vitro-and-in-vivo-pulmonary-fibrosis-by-modulating-the-interplay-of-fibrotic-matricelluar-proteins-and-cytokines
#2
Swarna Bale, Pooladanda Venkatesh, Manoj Sunkoju, Chandraiah Godugu
Pulmonary fibrosis (PF) is chronic lung disease with only two FDA approved clinically available drugs, with limited safety profile. Inadequate therapy motivated us to explore the effect of vimentin inhibitor Withaferin A, as an anti-fibrotic agent against TGF-β1-induced in vitro fibrotic events and Bleomycin induced in vivo fibrosis with an emphasis on epithelial to mesenchymal transition (EMT), extracellular matrix deposition (ECM), inflammation, and angiogenesis. In vitro EMT and fibrotic events were induced by TGF-β1 in alveolar epithelial cells and human fetal lung fibroblasts followed by treatment with Withaferin A (0...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29621624/astilbin-ameliorates-pulmonary-fibrosis-via-blockade-of-hedgehog-signaling-pathway
#3
Jie Zhang, Hanchen Liu, Chenguang Song, Jinjin Zhang, Youlei Wang, Changjun Lv, Xiaodong Song
BACKGROUND AND OBJECTIVE: The nature of pulmonary fibrosis involves inadequate repair of the epithelial cell barrier accompanied by impaired regulation of the fibroblast. Moreover, pulmonary fibrosis currently lacks an effective therapeutic drug. This study targets the protection of the epithelial cell and fibroblast to identify a novel, potentially therapeutic drug (i.e., astilbin). METHODS: In this study, the cytotoxicity of astilbin was firstly detected using CCK-8...
April 2, 2018: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29615497/novel-broadly-reactive-anticapsular-antibodies-against-carbapenem-resistant-klebsiella-pneumoniae-protect-from-infection
#4
Elizabeth Diago-Navarro, Michael P Motley, Gonzalo Ruiz-Peréz, Winnie Yu, Julianne Austin, Bruna M S Seco, Guozhi Xiao, Aniska Chikhalya, Peter H Seeberger, Bettina C Fries
Carbapenem-resistant (CR) sequence type 258 (ST258) Klebsiella pneumoniae has become an urgent health care threat, causing an increasing number of high-mortality infections. Its resistance to numerous antibiotics and threat to immunocompromised patients necessitate finding new therapies to combat these infections. Previous successes in the laboratory, as well as the conservation of capsular polysaccharide (CPS) among the members of the ST258 clone, suggest that monoclonal antibody (MAb) therapy targeting the outer polysaccharide capsule of K...
April 3, 2018: MBio
https://www.readbyqxmd.com/read/29592881/nano-engineered-mesenchymal-stem-cells-increase-therapeutic-efficacy-of-anticancer-drug-through-true-active-tumor-targeting
#5
Buddhadev Layek, Tanmoy Sadhukha, Jayanth Panyam, Swayam Prabha
Tumor-targeted drug delivery has the potential to improve therapeutic efficacy and mitigate non-specific toxicity of anticancer drugs. However, current drug delivery approaches rely on inefficient passive accumulation of the drug carrier in the tumor. We have developed a unique, truly active tumor targeting strategy that relies on engineering mesenchymal stem cells (MSCs) with drug-loaded nanoparticles. Our studies using the A549 orthotopic lung tumor model show that nano-engineered MSCs carrying the anticancer drug paclitaxel (PTX) home to tumors and create cellular drug depots that release the drug payload over several days...
March 28, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29589222/development-of-novel-octanoyl-chitosan-nanoparticles-for-improved-rifampicin-pulmonary-delivery-optimization-by-factorial-design
#6
Kailash C Petkar, Sandip Chavhan, N Kunda, I Saleem, S Somavarapu, Kevin M G Taylor, Krutika K Sawant
A novel hydrophobic chitosan derivative, octanoyl chitosan (OC) with improved organic solubility was synthesized, characterized, and employed for the preparation of rifampicin (Rif) encapsulated nanoparticle formulations for pulmonary delivery. OC was characterized to confirm acyl group substitution and cytotoxicity in A549 epithelial lung cells. OC nanoparticles were produced by the double emulsion solvent evaporation technique without cross-linking and characterized for particle size distribution, morphology, crystallinity, thermal stability, aerosol delivery, and drug release rate...
March 27, 2018: AAPS PharmSciTech
https://www.readbyqxmd.com/read/29550472/pentagalloyl-glucose-increases-elastin-deposition-decreases-reactive-oxygen-species-and-matrix-metalloproteinase-activity-in-pulmonary-fibroblasts-under-inflammatory-conditions
#7
Vaideesh Parasaram, Nasim Nosoudi, Aniqa Chowdhury, Naren Vyavahare
mphysema is characterized by degradation of lung alveoli that leads to poor airflow in lungs. Irreversible elastic fiber degradation by matrix metalloproteinases (MMPs) and reactive oxygen species (ROS) activity leads to loss of elasticity and drives the progression of this disease. We investigated if a polyphenol, pentagalloyl glucose (PGG) can increase elastin production in pulmonary fibroblasts. We also studied the effect of PGG treatment in reducing MMP activity and ROS levels in cells. We exposed rat pulmonary fibroblasts to two different types of inflammatory environments i...
March 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29541999/in-vitro-evaluation-of-the-inhalable-quercetin-loaded-nanoemulsion-for-pulmonary-delivery
#8
Noor Hafizah Arbain, Norazlinaliza Salim, Hamid Reza Fard Masoumi, Tin Wui Wong, Mahiran Basri, Mohd Basyaruddin Abdul Rahman
Bioavailability of quercetin, a flavonoid potentially known to combat cancer, is challenging due to hydrophobic nature. Oil-in-water (O/W) nanoemulsion system could be used as nanocarrier for quercertin to be delivered to lung via pulmonary delivery. The novelty of this nanoformulation was introduced by using palm oil ester/ricinoleic acid as oil phase which formed spherical shape nanoemulsion as measured by transmission electron microscopy and Zetasizer analyses. High energy emulsification method and D-optimal mixture design were used to optimize the composition towards the volume median diameter...
March 14, 2018: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/29536186/nebulization-of-cyclic-arginine-glycine-d-aspartic-acid-peptide-grafted-and-drug-encapsulated-liposomes-for-inhibition-of-acute-lung-injury
#9
Hari R Desu, Laura A Thoma, George C Wood
PURPOSE: Acute lung injury (ALI) is a fatal syndrome in critically ill patients. It is characterized by lung edema and inflammation. Numerous pro-inflammatory mediators are released into alveoli. Among them, interleukin-1beta (IL-1β) causes an increase in solute permeability across the alveolar-capillary barrier leading to edema. It activates key effector cells (alveolar epithelial and endothelial cells) releasing inflammatory chemokines and cytokines. The purpose of the study was to demonstrate that nebulized liposomes inhibit ALI in vivo...
March 13, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29499614/use-of-functional-respiratory-imaging-to-characterize-the-effect-of-inhalation-profile-and-particle-size-on-lung-deposition-of-inhaled-corticosteroid-long-acting-%C3%AE-2-agonists-delivered-via-a-pressurized-metered-dose-inhaler
#10
Cedric Van Holsbeke, Jan De Backer, Wim Vos, Jonathan Marshall
BACKGROUND: Functional respiratory imaging (FRI) uses three-dimensional models of human lungs and computational fluid dynamics to simulate functional changes within airways and predict the deposition of inhaled drugs. This study used FRI to model the effects of different patient inhalation and drug formulation factors on lung deposition of an inhaled corticosteroid/long-acting β2 -agonist (ICS/LABA) combination, administered by a pressurized metered-dose inhaler. METHODS: Three-dimensional models of the lungs of six patients with asthma (mean forced expiratory volume in 1 s, 83%), treated with an ICS/LABA, were included...
January 2018: Therapeutic Advances in Respiratory Disease
https://www.readbyqxmd.com/read/29493402/pharmacokinetics-of-salmeterol-and-fluticasone-propionate-delivered-in-combination-via-easyhaler-and-diskus-dry-powder-inhalers-in-healthy-subjects
#11
Merja Kirjavainen, Leena Mattila, Mikko Vahteristo, Jani Korhonen, Satu Lähelmä
BACKGROUND: Easyhaler® dry powder inhaler (DPI) containing salmeterol and fluticasone propionate was developed for the treatment of asthma and chronic obstructive pulmonary disease. Three different Salmeterol/fluticasone Easyhaler test products (Orion Pharma, Finland) were compared against the reference product Seretide® Diskus® DPI (GlaxoSmithKline, United Kingdom) to study whether any of the test products are bioequivalent with the reference. METHODS: Open and randomized pharmacokinetic four-period crossover study on 65 healthy volunteers was performed in a single center to compare the lung deposition and total systemic exposure of salmeterol and fluticasone propionate after administration of single doses (two inhalations of 50/500 μg/inhalation strength) in fasting conditions...
March 1, 2018: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/29486525/a-quasi-3d-compartmental-multi-scale-approach-to-detect-and-quantify-diseased-regional-lung-constriction-using-spirometry-data
#12
Ravishekar Ravi Kannan, Narender Singh, Andrzej Przekwas
Spirometry is a widely used pulmonary function test to detect the airflow limitations associated with various obstructive lung diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and even obesity-related complications. These conditions arise due to the change in the airway resistance, alveolar compliance, and inductance values. Currently, zero-dimensional (0D) compartmental models are commonly used for calibrating these resistance, compliance, and inductance values, i.e., solving the inverse spirometry problem...
February 27, 2018: International Journal for Numerical Methods in Biomedical Engineering
https://www.readbyqxmd.com/read/29468423/a-novel-method-for-studying-airway-hyperresponsiveness-in-allergic-guinea-pigs-in-vivo-using-the-preciseinhale-system-for-delivery-of-dry-powder-aerosols
#13
A J Lexmond, S Keir, W Terakosolphan, C P Page, B Forbes
Inhaled adenosine receptor agonists induce bronchoconstriction and inflammation in asthma and are used as bronchial challenge agents for the diagnosis of asthma and in respiratory drug development. Recently developed dry powder aerosols of adenosine have several advantages over nebulised adenosine 5'-monophosphate (AMP) as bronchial challenge agents. However, reverse translation of this bronchial challenge technique to pre-clinical drug development is limited by the difficulty of administering powder aerosols to animals...
February 21, 2018: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/29453801/regional-deposition-of-nasal-sprays-in-adults-a-wide-ranging-computational-study
#14
Milad Kiaee, Herbert Wachtel, Michelle L Noga, Andrew R Martin, Warren H Finlay
The present work examines regional deposition within the nose for nasal sprays over a large and wide ranging parameter space by using numerical simulation. A set of seven realistic adult nasal airway geometries was defined based on Computed Tomography (CT) images. Deposition in six regions of each nasal airway geometry (the vestibule, valve, anterior turbinate, posterior turbinate, olfactory, and nasopharynx) was determined for varying particle diameter, spray cone angle, spray release direction, particle injection speed, and particle injection location...
February 17, 2018: International Journal for Numerical Methods in Biomedical Engineering
https://www.readbyqxmd.com/read/29409488/the-topical-study-of-inhaled-drug-salbutamol-delivery-in-idiopathic-pulmonary-fibrosis
#15
Omar S Usmani, Martyn F Biddiscombe, Shuying Yang, Sally Meah, Eunice Oballa, Juliet K Simpson, William A Fahy, Richard P Marshall, Pauline T Lukey, Toby M Maher
BACKGROUND: Our aim was to investigate total and regional lung delivery of salbutamol in subjects with idiopathic pulmonary fibrosis (IPF). METHODS: The TOPICAL study was a 4-period, partially-randomised, controlled, crossover study to investigate four aerosolised approaches in IPF subjects. Nine subjects were randomised to receive 99mTechnetium-labelled monodisperse salbutamol (1.5 μm or 6 μm; periods 1 and 2). Subjects also received radio-labelled salbutamol using a polydisperse nebuliser (period 3) and unlabelled salbutamol (400 μg) using a polydisperse pressurized metered dose inhaler with volumatic spacer (pMDI; period 4)...
February 6, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29297393/substance-deposition-assessment-in-obstructed-pulmonary-system-through-numerical-characterization-of-airflow-and-inhaled-particles-attributes
#16
Antonios Lalas, Stavros Nousias, Dimitrios Kikidis, Aris Lalos, Gerasimos Arvanitis, Christos Sougles, Konstantinos Moustakas, Konstantinos Votis, Sylvia Verbanck, Omar Usmani, Dimitrios Tzovaras
BACKGROUND: Chronic obstructive pulmonary disease (COPD) and asthma are considered as the two most widespread obstructive lung diseases, whereas they affect more than 500 million people worldwide. Unfortunately, the requirement for detailed geometric models of the lungs in combination with the increased computational resources needed for the simulation of the breathing did not allow great progress to be made in the past for the better understanding of inflammatory diseases of the airways through detailed modelling approaches...
December 20, 2017: BMC Medical Informatics and Decision Making
https://www.readbyqxmd.com/read/29290827/local-intratracheal-delivery-of-perfluorocarbon-nanoparticles-to-lung-cancer-demonstrated-with-magnetic-resonance-multimodal-imaging
#17
Lina Wu, Xiaofei Wen, Xiance Wang, Chunan Wang, Xilin Sun, Kai Wang, Huiying Zhang, Todd Williams, Allen J Stacy, Junjie Chen, Anne H Schmieder, Gregory M Lanza, Baozhong Shen
Eighty percent of lung cancers originate as subtle premalignant changes in the airway mucosal epithelial layer of bronchi and alveoli, which evolve and penetrate deeper into the parenchyma. Liquid-ventilation, with perfluorocarbons (PFC) was first demonstrated in rodents in 1966 then subsequently applied as lipid-encapsulated PFC emulsions to improve pulmonary function in neonatal infants suffering with respiratory distress syndrome in 1996. Subsequently, PFC nanoparticles (NP) were extensively studied as intravenous (IV) vascular-constrained nanotechnologies for diagnostic imaging and targeted drug delivery applications...
2018: Theranostics
https://www.readbyqxmd.com/read/29180863/paclitaxel-and-quercetin-nanoparticles-co-loaded-in-microspheres-to-prolong-retention-time-for-pulmonary-drug-delivery
#18
Kang Liu, Weijuan Chen, Tingting Yang, Baofang Wen, Dejun Ding, Michael Keidar, Jinbao Tang, Weifen Zhang
High drug resistance, poor water solubility, short half-life, and low local drug concentration are obstacles for successful delivery of chemotherapeutic drugs for lung cancer. A new method involving the use of nanoparticles (NPs) for pulmonary delivery is proposed. However, use of NPs is limited by the particle size range for pulmonary drug delivery considering that NPs cannot be deposited directly into the lungs. NPs polymerized into microspheres (polymeric microspheres, PMs) will result in suitable particle sizes and retain the advantages of nanodrugs after redispersion when applied in pulmonary delivery...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29163164/lassbio-897-reduces-lung-injury-induced-by-silica-particles-in-mice-potential-interaction-with-the-a-2a-receptor
#19
Vinicius F Carvalho, Tatiana P T Ferreira, Ana C S de Arantes, François Noël, Roberta Tesch, Carlos M R Sant'Anna, Eliezer J L Barreiro, Carlos A M Fraga, Patrícia M Rodrigues E Silva, Marco A Martins
Silicosis is a lethal fibro-granulomatous pulmonary disease highly prevalent in developing countries, for which no proper therapy is available. Among a small series of N -acylhydrazones, the safrole-derived compound LASSBio-897 (3-thienylidene-3, 4-methylenedioxybenzoylhydrazide) raised interest due to its ability to bind to the adenosine A2A receptor. Here, we evaluated the anti-inflammatory and anti-fibrotic potential of LASSBio-897, exploring translation to a mouse model of silicosis and the A2A receptor as a site of action...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29150967/drug-delivery-strategies-for-chemoprevention-of-uvb-induced-skin-cancer-a-review
#20
REVIEW
Arvind Bagde, Arindam Mondal, Mandip Singh
Annually, more skin cancer cases are diagnosed than the collective incidence of the colon, lung, breast, and prostate cancer. Persistent contact with sunlight is a primary cause for all the skin malignancies. UVB radiation induces reactive oxygen species (ROS) production in the skin which eventually leads to DNA damage and mutation. Various delivery approaches for the skin cancer treatment/prevention have been evolving and are directed toward improvements in terms of delivery modes, therapeutic agents, and site-specificity of therapeutics delivery...
January 2018: Photodermatology, Photoimmunology & Photomedicine
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