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Dipicolinic acid as a novel spore-inspired excipient for antibody formulation

Publication date: 30 June 2017 Source:International Journal of Pharmaceutics, Volume 526, Issues 1–2 Author(s): Iris L. Batalha, Peng Ke, Esther Tejeda-Montes, Shahid Uddin, Christopher F. van der Walle, Graham Christie Ionic excipients are commonly used in aqueous therapeutic monoclonal antibody (mAb) formulations. Novel excipients are of industrial interest, with a recent focus on Arg salt forms and their application as viscosity reducing and stabilizing additives. Here, we report that the calcium salt of dipicolinic acid (DPA, pyridine-2,6-dicarboxylic acid), uniquely present in nature in the core of certain bacterial spores, reduces the viscosity of a mAb formulated at 150mg/mL, below that achieved by Arg hydrochloride at the same concentration (10mM). DPA also reduced the reversible phase separation of the same formulation, which characteristically occurs for this mAb upon cooling to 4°C. Differential scanning calorimetry and differential scanning fluorimetry did not reveal a conformation destabilisation of the mAb in the presence of 10mM DPA, or by the related quinolinic acid (QA, pyridine-2,3-dicarboxylic acid). However, fluorescence spectrophotometry did reveal localised (aromatic) conformational changes to the mAb attributed to DPA, dependent on the salt form. While precise mechanisms of action remain to be identified, our preliminary data suggest that these DPA salts are worthy of further investigation as novel ionic excipient for biologics formulation. G...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research

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Abstract Background: To evaluate USPIO labeling in different macrophage populations using a clinical 3.0T MR unit with optical and electron microscopy as the gold standard.Methods: Human monocytic cell line were differentiated into macrophages. Afterwards M0 macrophages were incubated with IL‐4 and IL‐13 in order to obtain M2 polarized macrophages or with IFN‐gamma and LPS for classical macrophage activation (M1). These groups were incubated with USPIO MR contrast agent (P904) for 36 hours; M0, M0+P904, M1+P904 and M2+P904 were analyzed in gel phantoms with a 3.0T MR scanner.Results: Micro‐RNA of M1 and M2 markers ...
Source: Journal of Cellular Physiology - Category: Cytology Authors: Tags: ORIGINAL RESEARCH ARTICLE Source Type: research
(University of Liverpool) A simple, non-invasive procedure that can indicate how long patients with cancer that has spread to the brain might survive and whether they are likely to respond to immunotherapy has been developed by researchers in Liverpool.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
There was an error in the D5-D95 in Figure  4 on page 179. The data has been corrected here. The correction to this parameter still supports the conclusion if the criteria of D5-D95 was taken as 7%.
Source: International Journal of Radiation Oncology * Biology * Physics - Category: Radiology Tags: Erratum Source Type: research
This study aims to explore whether nonalcoholic fatty liver disease (NAFLD) is a risk factor and a prognostic factor for pancreatic cancer. The study enrolled 557 patients (143 with and 414 without pancreatic cancer) who were diagnosed between January 2009 and December 2013. We reviewed the abdominal computed tomographic scans of the patients to confirm the diagnosis of NAFLD. Clinical parameters, laboratory data, and personal information were analyzed. NAFLD is an independent risk factor for pancreatic cancer according to adjusted multivariate logistic regression analysis (OR 2.63, 95% CI 1.24 –5.58,p = 0....
Source: Internal and Emergency Medicine - Category: Emergency Medicine Source Type: research
Publication date: 1 March 2018 Source:Carbohydrate Polymers, Volume 183 Author(s): Mao Yamagami, Hiroshi Kamitakahara, Arata Yoshinaga, Toshiyuki Takano This paper describes the design and synthesis of new trehalose-type diblock methylcellulose analogues with nonionic, cationic, and anionic cellobiosyl segments, namely 1-(tri-O-methyl-cellulosyl)-4-[β-d-glucopyranosyl-(1→4)-β-d-glucopyranosyloxymethyl]-1H-1,2,3-triazole (1), 1-(tri-O-methyl-cellulosyl)-4-[(6-amino-6-deoxy-β-d-glucopyranosyl)-(1→4)- 6-amino-6-deoxy-β-d-glucopyranosyloxymethyl]-1H-1,2,3-triazole (2), and 4-(tri-O-methyl-cellulo...
Source: Carbohydrate Polymers - Category: Biomedical Science Source Type: research
Publication date: November 2017 Source:Drug Discovery Today: Technologies, Volume 25 Author(s): Giulia Boscutti, Mickael Huiban, Jan Passchier The pharmaceutical industry is facing key challenges to improve return on R&D investment. Positron emission tomography (PET), by itself or in combination with complementary technologies such as magnetic resonance imaging (MRI), provides a unique opportunity to confirm a candidate’s ability to meet the so-called ‘three pillars’ of drug development. Positive confirmation provides confidence for go/no-go decision making at an early stage of the development proces...
Source: Drug Discovery Today: Technologies - Category: Drugs & Pharmacology Source Type: research
Publication date: November 2017 Source:Drug Discovery Today: Technologies, Volume 25 Author(s): Mehran Makvandi, Mark A. Sellmyer, Robert H. Mach Cancer and neurodegeneration represent two opposite ends of the biological spectrum but contain many common biological mechanisms. Two such mechanisms include the elevated levels of oxidative stress and DNA damage. In this brief review, we describe current approaches for imaging these biological pathways with the molecular imaging technique, Positron Emission Tomography (PET), and the potential of PET imaging studies to measure the efficacy of anticancer drugs and strategies for...
Source: Drug Discovery Today: Technologies - Category: Drugs & Pharmacology Source Type: research
We presented a rare diagnosis of pulsatile anterior neck swelling where a high riding brachiocephalic artery needs to be considered as a differential diagnosis. This 54-year-old lady presented with anterior neck swelling for one year which appear to be pulsatile, soft and non-tender mass. Ultrasound and Doppler scan, contrast-enhanced computed tomography (CECT) scan revealed that the neck swelling corresponds to the high riding brachiocephalic artery. Hence, ultrasound scan is essential to detect any vascular lesion prior to biopsy or fine needle aspiration cytology as to avoid catastrophic hemorrhage.
Source: Egyptian Journal of Ear, Nose, Throat and Allied Sciences - Category: ENT & OMF Source Type: research
Abstract B cells have recently entered the stage as an important accessory player in type 1 diabetes (T1D) etiopathogenesis. Experimental studies suggest regulatory functions of vitamin D on B cells. However, only a few human studies, with considerable methodological limitations, have been conducted within this field. Our objective was to investigate whether higher 25‐hydroxyvitamin D (25(OH)D) concentrations were inversely associated with β‐cell autoantigens glutamic acid decarboxylase (isoform 65) (GADA) and insulinoma‐associated antigen‐2A (IA‐2A). Further, we also wanted to examine the relationship betwe...
Source: Scandinavian Journal of Immunology - Category: Allergy & Immunology Authors: Tags: Human Immunology Source Type: research
Conclusion MonoE at low keV of venous contrast phase scans derived from a novel SDCT are suitable for the assessment of arteries in the abdomen and subsequent stenosis assessment. However, MonoE at 40keV constantly showed significant smaller luminal diameters than the corresponding conventional reconstructions (including the reference standard). This is possibly due to an improved differentiation of the vessel lumen from the wall and raises the question, which imaging technique should be used as an appropriate reference standard for vascular SDCT imaging studies.
Source: European Journal of Radiology - Category: Radiology Source Type: research
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