Read by QxMD icon Read

Pulmonary drug delivery animal model

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
Collin T Stabler, Shimon Lecht, Philip Lazarovici, Peter I Lelkes
INTRODUCTION: Mesenchymal stem cells (MSCs) of different biological sources are in Phase 1 clinical trials and are being considered for Phase 2 therapy of lung disorders, and lung (progenitor) cells derived from pluripotent stem cells (SCs) are under development in preclinical animal models. SOURCES OF DATA: and AREAS OF AGREEMENT: There is consensus about the therapeutic potential of transplanted SCs, mainly MSCs, primarily involves paracrine 'bystander' effects that confer protection of the epithelial and endothelial linings of the lung caused by inflammation and/or fibrosis and lead to increased survival in animal models...
September 2015: British Medical Bulletin
Lucila Garcia Contreras, Jean Sung, Mariam Ibrahim, Katharina Elbert, David Edwards, Anthony Hickey
Tuberculosis (TB) is a life-threatening infection that requires a lengthy treatment process that is often associated with adverse effects. Pulmonary delivery of anti-TB drugs has the potential to increase efficacy of treatment by increasing drug concentrations at the lungs, the primary site of infection. The aim of the present study is to evaluate the disposition of rifampicin (RIF) after its pulmonary administration as porous particles (PPs) to guinea pigs and contrast it to that after oral administration...
August 3, 2015: Molecular Pharmaceutics
Louise Organ, Barbara Bacci, Emmanuel Koumoundouros, Garry Barcham, Wayne Kimpton, Cameron J Nowell, Chrishan Samuel, Ken Snibson
BACKGROUND: Idiopathic Pulmonary fibrosis (IPF) is a fatal respiratory disease, characterized by a progressive fibrosis and worsening lung function. While the outcomes of recent clinical trials have resulted in therapies to slow the progression of the disease, there is still a need to develop alternative therapies, which are able to prevent fibrosis. AIM: This study uses a segmental lung infusion of bleomycin (BLM) to investigate pulmonary fibrosis in a physiologically relevant large animal species...
April 2015: Experimental Lung Research
Jacob S Brenner, Colin Greineder, Vladimir Shuvaev, Vladimir Muzykantov
INTRODUCTION: Even though pulmonary diseases are among the leading causes of morbidity and mortality in the world, exceedingly few life-prolonging therapies have been developed for these maladies. Relief may finally come from nanomedicine and targeted drug delivery. AREAS COVERED: Here, we focus on four conditions for which the pulmonary endothelium plays a pivotal role: acute respiratory distress syndrome, primary graft dysfunction occurring immediately after lung transplantation, pulmonary arterial hypertension and pulmonary embolism...
February 2015: Expert Opinion on Drug Delivery
Vinayak Shenoy, Kwang-Chul Kwon, Anandharajan Rathinasabapathy, Shina Lin, Guiying Jin, Chunjuan Song, Pollob Shil, Anand Nair, Yanfei Qi, Qiuhong Li, Joseph Francis, Michael J Katovich, Henry Daniell, Mohan K Raizada
Emerging evidences indicate that diminished activity of the vasoprotective axis of the renin-angiotensin system, constituting angiotensin-converting enzyme 2 (ACE2) and its enzymatic product, angiotensin-(1-7) [Ang-(1-7)] contribute to the pathogenesis of pulmonary hypertension (PH). However, long-term repetitive delivery of ACE2 or Ang-(1-7) would require enhanced protein stability and ease of administration to improve patient compliance. Chloroplast expression of therapeutic proteins enables their bioencapsulation within plant cells to protect against gastric enzymatic degradation and facilitates long-term storage at room temperature...
December 2014: Hypertension
M Carme Coll Ferrer, Vladimir V Shuvaev, Blaine J Zern, Russell J Composto, Vladimir R Muzykantov, David M Eckmann
Lysozyme dextran nanogels (NG) have great potential in vitro as a drug delivery platform, combining simple chemistry with rapid uptake and cargo release in target cells with "stealth" properties and low toxicity. In this work, we study for the first time the potential of targeted NG as a drug delivery platform in vivo to alleviate acute pulmonary inflammation in animal model of LPS-induced lung injury. NG are targeted to the endothelium via conjugation with an antibody (Ab) directed to Intercellular Adhesion Molecule-1(ICAM-NG), whereas IgG conjugated NG (IgG-NG) are used for control formulations...
2014: PloS One
Laurie A Manwell, Brittany Ford, Brittany A Matthews, Heather Heipel, Paul E Mallet
INTRODUCTION: Studies of the rewarding and addictive properties of cannabinoids using rodents as animal models of human behaviour often fail to replicate findings from human studies. Animal studies typically employ parenteral routes of administration, whereas humans typically smoke cannabis, thus discrepancies may be related to different pharmacokinetics of parenteral and pulmonary routes of administration. Accordingly, a novel delivery system of vapourized Δ(9)-tetrahydrocannabinol (Δ(9)-THC) was developed and assessed for its pharmacokinetic, pharmacodynamic, and behavioural effects in rodents...
July 2014: Journal of Pharmacological and Toxicological Methods
Amanda J Hayes, Shahnaz Bakand
INTRODUCTION: The human respiratory system is an important route for the entry of inhaled therapeutics into the body to treat diseases. Inhaled materials may consist of gases, vapours, aerosols and particulates. In all cases, assessing the toxicological effect of inhaled therapeutics has many challenges. AREAS COVERED: This article provides an overview of in vivo and in vitro models for testing the toxicity of inhaled therapeutics and nanoparticles implemented in drug delivery...
July 2014: Expert Opinion on Drug Metabolism & Toxicology
Mukta Paranjpe, Christel C Müller-Goymann
Colloidal drug delivery systems have been extensively investigated as drug carriers for the application of different drugs via different routes of administration. Systems, such as solid lipid nanoparticles, polymeric nanoparticles and liposomes, have been investigated for a long time for the treatment of various lung diseases. The pulmonary route, owing to a noninvasive method of drug administration, for both local and systemic delivery of an active pharmaceutical ingredient (API) forms an ideal environment for APIs acting on pulmonary diseases and disorders...
2014: International Journal of Molecular Sciences
Catherine W M Ong, Paul T Elkington, Jon S Friedland
Tuberculosis (TB), a chronic infectious disease of global importance, is facing the emergence of drug-resistant strains with few new drugs to treat the infection. Pulmonary cavitation, the hallmark of established disease, is associated with very high bacillary burden. Cavitation may lead to delayed sputum culture conversion, emergence of drug resistance, and transmission of the infection. The host immunological reaction to Mycobacterium tuberculosis is implicated in driving the development of TB cavities. TB is characterized by a matrix-degrading phenotype in which the activity of proteolytic matrix metalloproteinases (MMPs) is relatively unopposed by the specific tissue inhibitors of metalloproteinases...
July 1, 2014: American Journal of Respiratory and Critical Care Medicine
Lisa M Kaminskas, Victoria M McLeod, Gemma M Ryan, Brian D Kelly, John M Haynes, Mark Williamson, Neeranat Thienthong, David J Owen, Christopher J H Porter
Direct administration of chemotherapeutic drugs to the lungs significantly enhances drug exposure to lung resident cancers and may improve chemotherapy when compared to intravenous administration. Direct inhalation of uncomplexed or unencapsulated cytotoxic drugs, however, leads to bolus release and unacceptable lung toxicity. Here, we explored the utility of a 56kDa PEGylated polylysine dendrimer, conjugated to doxorubicin, to promote the controlled and prolonged exposure of lung-resident cancers to cytotoxic drug...
June 10, 2014: Journal of Controlled Release: Official Journal of the Controlled Release Society
Jeffry Weers, Thomas Tarara
Spray-dried PulmoSphere™ formulations comprise phospholipid-based small, porous particles. Drug(s) may be incorporated in or with PulmoSphere formulations in three formats: solution-, suspension-, and carrier-based systems. The multiple formats may be administered to the respiratory tract with multiple delivery systems, including portable inhalers (pressurized, metered-dose inhaler and dry-powder inhaler), nebulizers, and via liquid dose instillation in conjunction with partial liquid ventilation. The PulmoSphere platform (particles, formats, delivery systems) enables pulmonary delivery of a broad range of drugs independent of their physicochemical properties and lung dose...
March 2014: Therapeutic Delivery
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"