Powell L.C.,University of Cardiff |
Powell L.C.,University of Swansea |
Pritchard M.F.,University of Cardiff |
Pritchard M.F.,University of Swansea |
And 6 more authors.
American Journal of Respiratory Cell and Molecular Biology | Year: 2014
Pseudomonas aeruginosa (PA) biofilm-associated infections are a common cause of morbidity in chronic respiratory disease and represent a therapeutic challenge. Recently, the ability of a novel alginate oligomer (OligoG) to potentiate the effect of antibiotics against gram-negative, multi-drug-resistant bacteria and inhibit biofilm formation in vitro has been described. Interaction of OligoG with the cell surface of PA was characterized at the nanoscale using atomic force microscopy (AFM), zeta potential measurement (surface charge), and sizing measurements (dynamic light scattering). The ability of OligoG to modify motility was studied in motility assays. AFM demonstrated binding of OligoG to the bacterial cell surface, which was irreversible after exposure to hydrodynamic shear (5,500 × g). Zeta potential analysis (pH 5-9; 0.1-0.001 M NaCl) demonstrated that binding was associated with marked changes in the bacterial surface charge (-30.9±0.8 to -47.0 ± 2.3 mV; 0.01 M NaCl [pH 5]; P < 0.001). Sizing analysis demonstrated that alteration of surface charge was associated with cell aggregation with a 2- to 3-fold increase in mean particle size at OligoG concentrations greater than 2% (914 ± 284 to 2599 ± 472 nm; 0.01 M NaCl [pH 5]; P < 0.001). These changes were associated with marked dose-dependent inhibition in bacterial swarming motility in PA and Burkholderia spp. The ability of OligoG to bind to a bacterial surface, modulate surface charge, induce microbial aggregation, and inhibit motility represents important direct mechanisms by which antibiotic potentiation and biofilm disruption is affected. These results highlight the value of combining multiple nanoscale technologies to further our understanding of the mechanisms of action of novel antibacterial therapies. Copyright © 2014 by the American Thoracic Society.
Powell L.C.,University of Cardiff |
Powell L.C.,University of Swansea |
Sowedan A.,University of Swansea |
Khan S.,University of Cardiff |
And 6 more authors.
Biofouling | Year: 2013
The influence of a novel, safe antibiofilm therapy on the mechanical properties of Pseudomonas aeruginosa and Acinetobacter baumannii biofilms in vitro was characterized. A multiscale approach employing atomic force microscopy (AFM) and rheometry was used to quantify the mechanical disruption of the biofilms by a therapeutic polymer based on a low-molecular weight alginate oligosaccharide (OligoG). AFM demonstrated structural alterations in the biofilms exposed to OligoG, with significantly lower Young's moduli than the untreated biofilms, (149 MPa vs 242 MPa; p < 0.05), a decreased resistance to hydrodynamic shear and an increased surface irregularity (Ra) in the untreated controls (35.2 nm ± 7.6 vs 12.1 nm ± 5.4; p < 0.05). Rheology demonstrated that increasing clinically relevant concentrations of OligoG (<10%) were associated with an increasing phase angle (δ) over a wide range of frequencies (0.1-10 Hz). These results highlight the utility of these techniques for the study of three-dimensional biofilms and for quantifying novel disruption therapies in vitro. © 2013 Copyright Taylor and Francis Group, LLC.
News Article | November 10, 2016
ReportsnReports.com adds "Chronic Obstructive Pulmonary Disease (COPD) - Pipeline Review, H2 2016" to its store providing comprehensive information on the therapeutics under development for Chronic Obstructive Pulmonary Disease (COPD) (Respiratory), complete with analysis by stage of development, drug target, mechanism of action (MoA), route of administration (RoA) and molecule type. The guide covers the descriptive pharmacological action of the therapeutics, its complete research and development history and latest news and press releases. Complete report on H2 2016 pipeline review of Chronic Obstructive Pulmonary Disease (COPD) with 172 market data tables and 16 figures, spread across 577 pages is available at http://www.reportsnreports.com/reports/743409-chronic-obstructive-pulmonary-disease-copd-pipeline-review-h2-2016.html . Companies discussed in this Chronic Obstructive Pulmonary Disease (COPD) Pipeline Review, H2 2016 report include AB2 Bio Ltd., Abeona Therapeutics, Inc., Ache Laboratorios Farmaceuticos S/A, Achillion Pharmaceuticals, Inc., Adamis Pharmaceuticals Corporation, Advinus Therapeutics Ltd, AlgiPharma AS, Allinky Biopharma, Alteogen Inc., Amakem NV, Ampio Pharmaceuticals, Inc., Angion Biomedica Corp., Apellis Pharmaceuticals Inc, Aridis Pharmaceuticals LLC, Astellas Pharma Inc., AstraZeneca Plc, Asubio Pharma Co., Ltd., Axikin Pharmaceuticals, Inc., Bayer AG, Beech Tree Labs, Inc., Bioneer Corporation, Biotie Therapies Corp., Boehringer Ingelheim GmbH, C4X Discovery Holdings PLC, Carolus Therapeutics, Inc., Cellular Biomedicine Group, Inc., Chiesi Farmaceutici SpA, Circassia Pharmaceuticals Plc, CSL Limited, Cytokinetics, Inc., Daiichi Sankyo Company, Limited, Diffusion Pharmaceuticals Inc., Domainex Limited, Elsalys Biotech SAS, enGene, Inc, Errant Gene Therapeutics, LLC, F. Hoffmann-La Roche Ltd., Foresee Pharmaceuticals, LLC, Galapagos NV, Gilead Sciences, Inc., GlaxoSmithKline Plc, Hanmi Pharmaceuticals, Co. Ltd., iCeutica, Inc., InMed Pharmaceuticals Inc., Innate Pharma S.A., INVENT Pharmaceuticals, Inc., Invion Limited, Jiangsu Hansoh Pharmaceutical Co., Ltd., Johnson & Johnson, KaloBios Pharmaceuticals, Inc., Kissei Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Ligand Pharmaceuticals, Inc., Medestea Research & Production S.p.A., Merck & Co., Inc., Mereo Biopharma Group Plc, Meridigen Biotech Co., Ltd., Microbion Corporation, Novartis AG, Odan Laboratories Ltd., OPKO Health, Inc., Orion Oyj, Panmira Pharmaceuticals, LLC., Pfizer Inc., PharmaLundensis AB, Pharmaxis Limited, Pila Pharma AB, Polyphor Ltd., Promedior, Inc., ProMetic Life Sciences Inc., Proteostasis Therapeutics, Inc., Pulmagen Therapeutics LLP, Pulmatrix, Inc., Quark Pharmaceuticals, Inc., Re-Pharm Limited, Recipharm AB, Respira Therapeutics Inc, Respiratorius AB, rEVO Biologics, Inc., Rhizen Pharmaceuticals S.A., SATT North SAS, Selvita S.A., Seoul Pharma Co., Ltd., Spring Bank Pharmaceuticals, Inc., Stelic Institute & Co., Inc., sterna biologicals Gmbh & Co KG, Sucampo Pharmaceuticals, Inc., Sun Pharma Advanced Research Company Ltd., Sunovion Pharmaceuticals Inc., Synovo GmbH, Syntrix Biosystems, Inc., Takeda Pharmaceutical Company Limited, Teva Pharmaceutical Industries Ltd., TGV-Laboratories, Therabron Therapeutics, Inc., Theravance Biopharma, Inc., Torrent Pharmaceuticals Limited, U.S. Stem Cell, Inc., Unizyme Laboratories A/S, Vectura Group Plc, Verona Pharma Plc, Vertex Pharmaceuticals Incorporated, Yuhan Corporation, Yungjin Pharm. Co., Ltd. and Zambon Company S.p.A. The Chronic Obstructive Pulmonary Disease (COPD) (Respiratory) pipeline guide also reviews of key players involved in therapeutic development for Chronic Obstructive Pulmonary Disease (COPD) and features dormant and discontinued projects. The guide covers therapeutics under Development by Companies /Universities /Institutes, the molecules developed by Companies in Pre-Registration, Filing rejected/Withdrawn, Phase III, Phase II, Phase I, Preclinical, Discovery and Unknown stages are 4, 1, 13, 40, 29, 81, 25 and 5 respectively for Similarly, the Universities portfolio in Preclinical and Discovery stages comprises 5 and 3 molecules, respectively for Chronic Obstructive Pulmonary Disease (COPD). Chronic Obstructive Pulmonary Disease (COPD) (Respiratory) pipeline guide helps in identifying and tracking emerging players in the market and their portfolios, enhances decision making capabilities and helps to create effective counter strategies to gain competitive advantage. The guide is built using data and information sourced from Global Markets Direct’s proprietary databases, company/university websites, clinical trial registries, conferences, SEC filings, investor presentations and featured press releases from company/university sites and industry-specific third party sources. Additionally, various dynamic tracking processes ensure that the most recent developments are captured on a real time basis. The report helps in identifying and tracking emerging players in the market and their portfolios, enhances decision making capabilities and helps to create effective counter strategies to gain competitive advantage. 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PubMed | Bio Images Drug Delivery Ltd., Gartnavel Hospital, Childrens Hospital for Wales, AlgiPharma AS and 2 more.
Type: Journal Article | Journal: Molecular pharmaceutics | Year: 2016
The host- and bacteria-derived extracellular polysaccharide coating of the lung is a considerable challenge in chronic respiratory disease and is a powerful barrier to effective drug delivery. A low molecular weight 12-15-mer alginate oligosaccharide (OligoG CF-5/20), derived from plant biopolymers, was shown to modulate the polyanionic components of this coating. Molecular modeling and Fourier transform infrared spectroscopy demonstrated binding between OligoG CF-5/20 and respiratory mucins. Ex vivo studies showed binding induced alterations in mucin surface charge and porosity of the three-dimensional mucin networks in cystic fibrosis (CF) sputum. Human studies showed that OligoG CF-5/20 is safe for inhalation in CF patients with effective lung deposition and modifies the viscoelasticity of CF-sputum. OligoG CF-5/20 is the first inhaled polymer therapy, represents a novel mechanism of action and therapeutic approach for the treatment of chronic respiratory disease, and is currently in Phase IIb clinical trials for the treatment of CF.
Khan S.,University of Cardiff |
Tondervik A.,Sintef |
Sletta H.,Sintef |
Klinkenberg G.,Sintef |
And 7 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2012
The uncontrolled, often inappropriate use of antibiotics has resulted in the increasing prevalence of antibiotic-resistant pathogens, with major cost implications for both United States and European health care systems. We describe the utilization of a low-molecular-weight oligosaccharide nanomedicine (OligoG), based on the biopolymer alginate, which is able to perturb multidrug-resistant (MDR) bacteria by modulating biofilm formation and persistence and reducing resistance to antibiotic treatment, as evident using conventional and robotic MIC screening and microscopic analyses of biofilm structure. OligoG increased (up to 512-fold) the efficacy of conventional antibiotics against important MDR pathogens, including Pseudomonas, Acinetobacter, and Burkholderia spp., appearing to be effective with several classes of antibiotic (i.e., macrolides, β-lactams, and tetracyclines). Using confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM), increasing concentrations (2%, 6%, and 10%) of alginate oligomer were shown to have a direct effect on the quality of the biofilms produced and on the health of the cells within that biofilm. Biofilm growth was visibly weakened in the presence of 10% OligoG, as seen by decreased biomass and increased intercellular spaces, with the bacterial cells themselves becoming distorted and uneven due to apparently damaged cell membranes. This report demonstrates the feasibility of reducing the tolerance of wound biofilms to antibiotics with the use of specific alginate preparations. Copyright © 2012, American Society for Microbiology. All Rights Reserved.