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Pulmonary drug delivery animal model

Arul Prakash Francis, Thiyagarajan Devasena
Carbon nanotubes (CNTs) are widely used in the aerospace, automotive, and electronics industries because of their stability, enhanced metallic, and electrical properties. CNTs are also being investigated for biomedical applications such as drug delivery systems and biosensors. However, the toxic potential of CNTs was reported in various cell lines and animal models. The toxicity depends on diverse properties of the CNTs, such as length, aspect ratio, surface area, degree of aggregation, purity, concentration, and dose...
January 1, 2018: Toxicology and Industrial Health
Hamed Vakilzadeh, Jaleh Varshosaz, Mohsen Minaiyan
INTRODUCTION: Triptorelin the synthetic analog of gonadotrophin-releasing hormone is used for treatment of sex hormone dependent diseases via parenteral administration. The aim of the present study was investigation the possibility of triptorelin pulmonary delivery and preparation of a pulmonary nanocarrier delivery system for it. METHODS: Triptorelin was loaded in Pluronic-F127 grafted poly (methyl vinyl ether-alt-maleic acid) nanomicelles by direct dissolution method...
February 8, 2018: Current Drug Delivery
Robert P Erickson, Gail Deutsch, Ruturaj Patil
We have tested the efficacy of hydroxypropyl-beta-cyclodextrin (HPBCD) delivered by the nasal route in the mouse model of juvenile Niemann-Pick C1 disease (NPC1), as pulmonary disease has not responded to systemic therapy with this drug. Since mice have no gag reflex, coating of the nasal cavity, with possible access to the brain, would be followed by delivery of HPBCD to the lung. While foamy macrophages, containing stored cholesterol, were found in the Npc1 nmf164 homozygous mice, a marked inflammatory response was found with inhaled HPBCD, both in mutant and wild-type animals...
February 6, 2018: Journal of Applied Genetics
Sara I Ruiz, Larry E Bowen, Mark M Bailey, Cory Berkland
Burkholderia pseudomallei, the etiological agent responsible for melioidosis, exhibits a great public health toll in its endemic regions. The elevation of B. pseudomallei to a Tier I select agent underscores the urgent need for effective therapeutics and preventatives. The current treatment regimen for melioidosis is suboptimal, requiring an intensive phase of intravenous antibiotic followed by months of oral antibiotics. Inhaled antibiotics are a promising avenue to pursue for pulmonary diseases, including melioidosis, since this mode of delivery mimics the likely exposure route and can provide high drug doses directly to the infected tissue...
March 5, 2018: Molecular Pharmaceutics
A Guillon, T Sécher, L A Dailey, L Vecellio, M de Monte, M Si-Tahar, P Diot, C P Page, N Heuzé-Vourc'h
Acute and chronic respiratory diseases account for major causes of illness and deaths worldwide. Recent developments of biotherapeutics opened a new era in the treatment and management of patients with respiratory diseases. When considering the delivery of therapeutics, the inhaled route offers great promises with a direct, non-invasive access to the diseased organ and has already proven efficient for several molecules. To assist in the future development of inhaled biotherapeutics, experimental models are crucial to assess lung deposition, pharmacokinetics, pharmacodynamics and safety...
January 30, 2018: International Journal of Pharmaceutics
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
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
Phillip G Durham, Shumaila N Hanif, Lucia Garcia Contreras, Ellen F Young, Miriam S Braunstein, Anthony J Hickey
Development of new therapeutic products requires efficacy testing in an animal model. The pulmonary route of administration can be utilized to deliver drugs locally and systemically. Evaluation of dry powder aerosols necessitates an efficient dispersion mechanism to maintain high concentrations in an exposure chamber or for direct endotracheal administration. While solutions exist to expose animals by passive inhalation to dry powder aerosols, most require masses of powder in large excess of the dose delivered...
March 30, 2017: Journal of Visualized Experiments: JoVE
Jacob S Brenner
After dozens of clinical trials, there are still no Food and Drug Administration-approved drugs that improve mortality in acute respiratory distress syndrome (ARDS). These poor results may be caused in part by three unique pharmacological challenges presented by ARDS: (1) Patients with ARDS are fragile because of concomitant multiple organ dysfunction, so they do not tolerate off-target side effects of drugs; (2) inhaled drug delivery is impeded by the column of proteinaceous fluid covering the injured alveoli; and (3) ARDS is heterogeneous in its underlying pathophysiology, so targeting one pathway is unlikely to improve most patients...
April 2017: Annals of the American Thoracic Society
Michael F Cuccarese, J Matthew Dubach, Christina Pfirschke, Camilla Engblom, Christopher Garris, Miles A Miller, Mikael J Pittet, Ralph Weissleder
Involvement of the immune system in tumour progression is at the forefront of cancer research. Analysis of the tumour immune microenvironment has yielded a wealth of information on tumour biology, and alterations in some immune subtypes, such as tumour-associated macrophages (TAM), can be strong prognostic indicators. Here, we use optical tissue clearing and a TAM-targeting injectable fluorescent nanoparticle (NP) to examine three-dimensional TAM composition, tumour-to-tumour heterogeneity, response to colony-stimulating factor 1 receptor (CSF-1R) blockade and nanoparticle-based drug delivery in murine pulmonary carcinoma...
February 8, 2017: Nature Communications
Jie Wang, Li Zhang, Lijuan Wang, Zhonghong Liu, Yu Yu
Our study aims to determine the metabolism and excretion of novel pulmonary-targeting docetaxel liposome (DTX-LP) using the in vitro and in vivo animal experimental models. The metabolism and excretion of DTX-LP and intravenous DTX (DTX-IN) in New Zealand rabbits were determined with ultraperformance liquid chromatography tandem mass spectrometry. We found DTX-LP and DTX-IN were similarly degraded in vitro by liver homogenates and microsomes, but not metabolized by lung homogenates. Ultra-performance liquid chromatography tandem mass spectrometry identified two shared DTX metabolites...
January 2017: Korean Journal of Physiology & Pharmacology
Jaume Aguero, Lahouaria Hadri, Nadjib Hammoudi, Lauren Leonardson, Roger J Hajjar, Kiyotake Ishikawa
Chronic pulmonary hypertension (PH) is associated with right ventricular failure and high mortality regardless of the underlying disease. Currently, therapies can improve clinical outcomes in specific subsets of patients, but have little impact on the progression of pulmonary vascular remodeling. Upon new advances in vector development and delivery techniques, gene therapy is a novel strategy in this field with the potential of overcoming the main limitations of approved drug therapies: modulation of novel anti-remodeling targets and selective pulmonary vasculature targeting with minimal systemic effects...
2017: Methods in Molecular Biology
Qian Zhong, Elizabeth R Bielski, Leonan S Rodrigues, Matthew R Brown, Joshua J Reineke, Sandro R P da Rocha
Lung is one of the most common sites to which almost all other primary tumors metastasize. The major challenges in the chemotherapy of lung metastases include the low drug concentration found in the tumors and high systemic toxicity upon systemic administration. In this study, we combine local lung delivery and the use of nanocarrier-based systems for improving pharmacokinetics and biodistribution of the therapeutics to fight lung metastases. We investigate the impact of the conjugation of doxorubicin (DOX) to carboxyl-terminated poly(amidoamine) dendrimers (PAMAM) through a bond that allows for intracellular-triggered release, and the effect of pulmonary delivery of the dendrimer-DOX conjugate in decreasing tumor burden in a lung metastasis model...
July 5, 2016: Molecular Pharmaceutics
Aateka Patel, A Woods, Yanira Riffo-Vasquez, Anna Babin-Morgan, Marie-Christine Jones, Stuart Jones, Kavitha Sunassee, Stephen Clark, Rafael T M de Rosales, Clive Page, Domenico Spina, Ben Forbes, Lea Ann Dailey
Lipid nanocapsules (LNCs) are semi-rigid spherical capsules with a triglyceride core that present a promising formulation option for the pulmonary delivery of drugs with poor aqueous solubility. Whilst the biodistribution of LNCs of different size has been studied following intravenous administration, the fate of LNCs following pulmonary delivery has not been reported. We investigated quantitatively whether lung inflammation affects the clearance of 50nm lipid nanocapsules, or is exacerbated by their pulmonary administration...
August 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Susanne R Youngren-Ortiz, Nishant S Gandhi, Laura España-Serrano, Mahavir B Chougule
This article reviews the pulmonary route of administration, aerosol delivery devices, characterization of pulmonary drug delivery systems, and discusses the rationale for inhaled delivery of siRNA. Diseases with known protein malfunctions may be mitigated through the use of siRNA therapeutics. The inhalation route of administration provides local delivery of siRNA therapeutics for the treatment of various pulmonary diseases, however barriers to pulmonary delivery and intracellular delivery of siRNA exists. siRNA loaded nanocarriers can be used to overcome the barriers associated with the pulmonary route, such as anatomical barriers, mucociliary clearance, and alveolar macrophage clearance...
February 28, 2016: Kona: Powder Science and Technology in Japan
Kohei Togami, Sumio Chono, Hitoshi Tada
Idiopathic pulmonary fibrosis is a lethal lung disease that is characterized by the accumulation of extracellular matrix and a change in lung structure. In this study, intrapulmonary pharmacokinetics of aerosolized model compounds were evaluated using rats with bleomycin-induced pulmonary fibrosis. Aerosol formulations of indocyanine green, 6-carboxyfluorescein (6-CF), and fluorescein isothiocyanate dextrans (FD; 4.4, 10, 70, and 250 kDa) were administered to rat lungs using a MicroSprayer. Indocyanine green fluorescence signals were significantly weaker in fibrotic lungs than in control lungs and 6-CF and FD concentrations in the plasma of pulmonary fibrotic animals were markedly higher than in the plasma of control animals...
March 2016: Journal of Pharmaceutical Sciences
Gemma M Ryan, Robert J Bischof, Perenlei Enkhbaatar, Victoria M McLeod, Linda J Chan, Seth A Jones, David J Owen, Christopher J H Porter, Lisa M Kaminskas
PURPOSE: Cancer metastasis to pulmonary lymph nodes dictates the need to deliver chemotherapeutic and diagnostic agents to the lung and associated lymph nodes. Drug conjugation to dendrimer-based delivery systems has the potential to reduce toxicity, enhance lung retention and promote lymphatic distribution in rats. The current study therefore evaluated the pharmacokinetics and lung lymphatic exposure of a PEGylated dendrimer following inhaled administration. METHODS: Plasma pharmacokinetics and disposition of a 22 kDa PEGylated dendrimer were compared after aerosol administration to rats and sheep...
February 2016: Pharmaceutical Research
Claudia Meindl, Sandra Stranzinger, Neira Dzidic, Sharareh Salar-Behzadi, Stefan Mohr, Andreas Zimmer, Eleonore Fröhlich
BACKGROUND: Pulmonary drug delivery is characterized by short onset times of the effects and an increased therapeutic ratio compared to oral drug delivery. This delivery route can be used for local as well as for systemic absorption applying drugs as single substance or as a fixed dose combination. Drugs can be delivered as nebulized aerosols or as dry powders. A screening system able to mimic delivery by the different devices might help to assess the drug effect in the different formulations and to identify potential interference between drugs in fixed dose combinations...
2015: PloS One
Meenal Datta, Laura E Via, Wei Chen, James W Baish, Lei Xu, Clifton E Barry, Rakesh K Jain
Pulmonary granulomas--the hallmark of Mycobacterium tuberculosis (MTB) infection--are dense cellular lesions that often feature regions of hypoxia and necrosis, partially due to limited transport of oxygen. Low oxygen in granulomas can impair the host immune response, while MTB are able to adapt and persist in hypoxic environments. Here, we used a physiologically based mathematical model of oxygen diffusion and consumption to calculate oxygen profiles within the granuloma, assuming Michaelis-Menten kinetics...
April 2016: Annals of Biomedical Engineering
Chia-Lang Fang, Chih-Jen Wen, Ibrahim A Aljuffali, Calvin T Sung, Chun-Lin Huang, Jia-You Fang
A novel nanovesicle carrier, phosphatiosomes, was developed to enhance the targeting efficiency of phosphodiesterase 4 (PDE4) inhibitor to the lungs for treating acute lung injury (ALI) by intravenous administration. Phosphatiosomes were the basis of a niosomal system containing phosphatidylcholine (PC) and distearoylphosphatidylethanolamine polyethylene glycol (DSPE-PEG). Rolipram was used as the model drug loaded in the phosphatiosomes. Bioimaging, biodistribution, activated neutrophil inhibition, and ALI treatment were performed to evaluate the feasibility of phosphatiosomes as the lung-targeting carriers...
September 10, 2015: Journal of Controlled Release: Official Journal of the Controlled Release Society
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