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protein formulation,biopharmaceuticals

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https://www.readbyqxmd.com/read/29141152/tm-values-and-unfolded-fraction-can-predict-aggregation-rates-for-gcsf-variant-formulations-but-not-under-predominantly-native-conditions
#1
Mathew J Robinson, Paul Matejtschuk, Adrian F Bristow, Paul A Dalby
Protein engineering and formulation optimisation strategies can be taken to minimise protein aggregation in the biopharmaceutical industry. Short-term stability measures such as the mid-point transition temperature (Tm) for global unfolding provide convenient surrogates for longer-term (eg 2-year) degradation kinetics, with which to optimise formulations on practical time-scales. While successful in some cases, their limitations have not been fully evaluated or understood. Tm values are known to correlate with chemical degradation kinetics for wild-type granulocyte colony stimulating factor (GCSF) at pH 4-5...
November 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29059588/enablement-of-the-direct-analysis-of-excipients-in-monoclonal-antibody-formulations-through-the-incorporation-of-a-wide-pore-c18-protein-trap-with-hydrophilic-interaction-liquid-chromatography
#2
Jason Z Huang, Shujie Lin, Zongyun Huang, Mark S Bolgar
Establishing and maintaining the correct formulation composition is essential for ensuring the stability of biopharmaceutical drug products. A barrier to the routine assessment of excipient concentration is the lack of convenient and robust methods for the direct analysis of solutions containing high protein concentrations. To address this need an HPLC method was developed utilizing a wide-pore C18 guard column to trap proteins in-line with a hydrophilic interaction liquid chromatographic column to separate excipients...
October 16, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28993217/mechanistic-pbpk-modeling-of-the-dissolution-and-food-effect-of-a-bcs-iv-compound-the-venetoclax-story
#3
Arian Emami Riedmaier, David J Lindley, Jeffrey A Hall, Steven Castleberry, Russell T Slade, Patricia Stuart, Robert A Carr, Thomas B Borchardt, Daniel A J Bow, Marjoleen Nijsen
PURPOSE: Venetoclax, a selective B-cell lymphoma-2 inhibitor, is a biopharmaceutics classification system (BCS) class IV compound. The aim of this study was to develop a physiologically-based pharmacokinetic (PBPK) model to mechanistically describe absorption and disposition of an amorphous solid dispersion (ASD) formulation of venetoclax in humans. METHODS: A mechanistic PBPK model was developed incorporating measured amorphous solubility, dissolution, metabolism and plasma protein binding...
October 6, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28939518/trimethylamine-n-oxide-tmao-is-a-counteracting-solute-of-benzyl-alcohol-for-multi-dose-formulation-of-immunoglobulin
#4
Shunsuke Yoshizawa, Shogo Oki, Tsutomu Arakawa, Kentaro Shiraki
Multi-dose formulation of biopharmaceuticals contains an antimicrobial preservative, which may facilitate aggregation of the proteins due to their hydrophobic protein binding. Here, we have investigated the effects of co-solvents on heat-induced protein aggregation in the presence of an antimicrobial preservative. Human immunoglobulin G (IgG) and benzyl alcohol were chosen because of their wide usage as a pharmaceutical protein and a preservative. Trimethylamine N-oxide (TMAO) was found to be the most effective additive in suppressing benzyl alcohol-induced IgG aggregation among the additives tested...
September 20, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28917988/a-comprehensive-screening-platform-for-aerosolizable-protein-formulations-for-intranasal-and-pulmonary-drug-delivery
#5
Martina Röhm, Stefan Carle, Frank Maigler, Johannes Flamm, Viktoria Kramer, Chrystelle Mavoungou, Otmar Schmid, Katharina Schindowski
Aerosolized administration of biopharmaceuticals to the airways is a promising route for nasal and pulmonary drug delivery, but - in contrast to small molecules - little is known about the effects of aerosolization on safety and efficacy of biopharmaceuticals. Proteins are sensitive against aerosolization-associated shear stress. Tailored formulations can shield proteins and enhance permeation, but formulation development requires extensive screening approaches. Thus, the aim of this study was to develop a cell-based in vitro technology platform that includes screening of protein quality after aerosolization and transepithelial permeation...
September 14, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28865117/development-of-a-general-defined-medium-for-pichia-pastoris
#6
Catherine B Matthews, Angel Kuo, Kerry R Love, J Christopher Love
Pichia pastoris is widely used as a host for recombinant protein production. More than 500 proteins have been expressed in the organism at a variety of cultivation scales, from small shake flasks to large bioreactors. Large-scale fermentation strategies typically employ chemically defined growth medium because of its greater batch-to-batch consistency and in many cases, lower costs compared to complex medium. For biopharmaceuticals, defined growth medium may also simplify downstream purification and regulatory documentation...
September 2, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28818376/an-overview-on-the-strategies-to-exploit-rice-endosperm-as-production-platform-for-biopharmaceuticals
#7
REVIEW
Fumio Takaiwa, Yuhya Wakasa, Shimpei Hayashi, Taiji Kawakatsu
Cereal seed has been utilized as production platform for high-value biopharmaceutical proteins. Especially, protein bodies (PBs) in seeds are not only natural specialized storage organs of seed storage proteins (SSPs), but also suitable intracellular deposition compartment for recombinant proteins. When various recombinant proteins were produced as secretory proteins by attaching N terminal ER signal peptide and C terminal KDEL endoplasmic reticulum (ER) retention signal or as fusion proteins with SSPs, high amounts of recombinant proteins can be predominantly accumulated in the PBs...
October 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28716374/high-throughput-quantitation-of-fc-containing-recombinant-proteins-in-cell-culture-supernatant-by-fluorescence-polarization-spectroscopy
#8
Ben Thompson, Jerry Clifford, Mike Jenns, Andrew Smith, Ray Field, Kalpana Nayyar, David C James
Measurement of recombinant protein product titer critically underpins all biopharmaceutical manufacturing process development, as well as diverse research and discovery activity. Here, we describe a simple rapid (<2 min per 96 samples) 96-well microplate-based assay that enables high-throughput quantitation of recombinant immunoglobulin G and Fc-containing IgG derivatives in mammalian cell culture supernatant over a wide dynamic range of 2.5-80 mg/L, using microplate fluorescence polarization (FP) spectroscopy...
October 1, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28699244/biophysical-characterization-of-layer-by-layer-synthesis-of-aptamer-drug-microparticles-for-enhanced-cell-targeting
#9
Kei X Tan, Michael K Danquah, Amandeep Sidhu, Sie Yon Lau, Clarence M Ongkudon
Targeted delivery of drug molecules to specific cells in mammalian systems demonstrates a great potential to enhance the efficacy of current pharmaceutical therapies. Conventional strategies for pharmaceutical delivery are often associated with poor therapeutic indices and high systemic cytotoxicity, and this results in poor disease suppression, low surviving rates, and potential contraindication of drug formulation. The emergence of aptamers has elicited new research interests into enhanced targeted drug delivery due to their unique characteristics as targeting elements...
July 11, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28649842/lipo-oligomer-nanoformulations-for-targeted-intracellular-protein-delivery
#10
Peng Zhang, Benjamin Steinborn, Ulrich Lächelt, Stefan Zahler, Ernst Wagner
Here, we report novel lipo-oligoaminoamide nanoformulations for targeted intracellular protein delivery. Formulations are generated by first bioreversibly conjugating a sequence-defined amphiphilic lipo-oligomer 728 to the cargo protein via disulfide bonds, followed by formulation of the formed 728-SS-protein conjugate with different helper lipids in various compositions. The triblock oligoaminoamide 728 contains cysteines for reversible covalent protein conjugation and cross-link-stabilization of formed nanoparticles, polyethylene glycol (PEG) for shielding, and providing a hydrophilic domain, eight cationizable succinoyl tetraethylene pentamine (Stp) repeats for endosomal buffering and escape into the cytosol, and a tetra-oleic acid block for hydrophobic stabilization...
July 10, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28625725/closing-the-gap-counting-and-sizing-of-particles-across-submicron-range-by-flow-cytometry-in-therapeutic-protein-products
#11
Liling Zhang, Shuai Shi, Valentyn Antochshuk
Quantification and size distribution characterization of subvisible particles in parenteral biopharmaceutics, present as both proteinaceous and nonproteinaceous particles in the size range from 0.1 to 100 μm, are important for biopharmaceutical industry due to their potential safety and efficacy implications. Although a number of analytical techniques are available to count and size subvisible particles, characterization of particles ≤2 μm remains a significant challenge due to technical limitations of existing particle counting instruments...
June 15, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28624419/thermo-optical-protein-characterization-for-straightforward-preformulation-development
#12
Randy Wanner, Dennis Breitsprecher, Stefan Duhr, Philipp Baaske, Gerhard Winter
The determination of protein unfolding and aggregation characteristics during preformulation is of major significance for the development of biopharmaceuticals. The aim of this study was to investigate the feasibility of a new immobilization- and label-free thermo-optical approach as an orthogonal method for material and time-saving early formulation and drugability screenings. In the experimental setup used, changes in the intrinsic tryptophan fluorescence of the protein were measured during IR laser-induced heating of the samples...
June 15, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28617076/characterization-of-highly-concentrated-antibody-solution-a-toolbox-for-the-description-of-protein-long-term-solution-stability
#13
Marie-Therese Schermeyer, Anna K Wöll, Bas Kokke, Michel Eppink, Jürgen Hubbuch
High protein titers are gaining importance in biopharmaceutical industry. A major challenge in the development of highly concentrated mAb solutions is their long-term stability and often incalculable viscosity. The complexity of the molecule itself, as well as the various molecular interactions, make it difficult to describe their solution behavior. To study the formulation stability, long- and short-range interactions and the formation of complex network structures have to be taken into account. For a better understanding of highly concentrated solutions, we combined established and novel analytical tools to characterize the effect of solution properties on the stability of highly concentrated mAb formulations...
October 2017: MAbs
https://www.readbyqxmd.com/read/28593474/high-throughput-prediction-approach-for-monoclonal-antibody-aggregation-at-high-concentration
#14
Mitja Zidar, Ana Šušterič, Miha Ravnik, Drago Kuzman
PURPOSE: Characterization of the monoclonal antibody aggregation process and identification of stability factors that could be used as indicators of aggregation propensity with an emphasis on a large number of samples and low protein material consumption. METHODS: Differential scanning calorimetry, dynamic light scattering and size exclusion chromatography were used as the main methodological approaches. Conformational stability, colloidal stability and aggregation kinetics were assessed for two different IgG monoclonal antibody (mAbs) subclasses...
September 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28496465/effect-of-nonionic-surfactants-dodecyl-maltoside-and-polysorbate-20-on-prevention-of-aggregation-and-conformational-changes-of-recombinant-human-ifn%C3%AE-_1b-induced-by-light
#15
Najmeh Mahjoubi, Ahmad Fazeli, Rassoul Dinarvand, Mohammad Reza Khoshayand, Maryam Shekarchi, Mohammad Reza Fazeli
Liquid protein formulations are prone to form aggregates. The effect of nonionic surfactants such as Polysorbate 20 (PS 20) and n-Dodecyl β-D-maltoside (DDM) on the prevention of aggregation and conformational changes of recombinant human IFNβ-1b (rhIFN β_1b) was explored. Polysorbate has been used in formulations of protein pharmaceuticals. There have been concerns about using PS 20 due to its residual peroxide content which may negatively affect protein efficacy. n-Dodecyl β-D-maltoside has been of interest and shown to be highly effective in prevention of aggregation...
2017: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/28476626/nile-red-fluorescence-spectrum-decomposition-enables-rapid-screening-of-large-protein-aggregates-in-complex-biopharmaceutical-formulations-like-influenza-vaccines
#16
Ziya Sahin, Senem Akkoc, Ronald Neeleman, Jonathan Haines, Veysel Kayser
The extensive presence of large (high molecular weight) protein aggregates in biopharmaceutical formulations is a concern for formulation stability and possibly safety. Tests to screen large aggregate content in such bioformulations are therefore needed for rapid and reliable quality control in industrial settings. Herein, non-commercial seasonal influenza split-virus vaccine samples, produced using various strains and extracted from selected industrial processing steps, were used as model complex bioformulations...
May 2, 2017: Vaccine
https://www.readbyqxmd.com/read/28440620/water-proton-nmr-a-tool-for-protein-aggregation-characterization
#17
Marc B Taraban, Roberto A DePaz, Brian Lobo, Y Bruce Yu
Formulation stability is a critical attribute of any protein-based biopharmaceutical drug due to a protein's inherent tendency to aggregate. Advanced analytical techniques currently used for characterization of protein aggregates are prone to a number of limitations and usually require additional manipulations with the sample, such as dilution, separation, labeling, and use of special cuvettes. In the present work, we compared conventional techniques for the analysis of protein aggregates with a novel approach that employs the water proton transverse relaxation rate R2((1)H2O)...
May 3, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28342056/formulation-delivery-and-stability-of-bone-morphogenetic-proteins-for-effective-bone-regeneration
#18
REVIEW
Inas El Bialy, Wim Jiskoot, M Reza Nejadnik
Bone morphogenetic proteins (BMPs) are responsible for bone formation during embryogenesis and bone regeneration and remodeling. The osteoinductive action of BMPs, especially BMP-2 and BMP-7, has led to their use in a range of insurmountable treatments where intervention is required for effective bone regeneration. Introduction of BMP products to the market, however, was not without reports of multiple complications and side effects. Aiming for optimization of the therapeutic efficacy and safety, efforts have been focused on improving the delivery of BMPs to lower the administered dose, localize the protein, and prolong its retention time at the site of action...
June 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28341309/polymorphic-distribution-of-proteins-in-solution-by-mass-spectrometry-the-analysis-of-insulin-analogues
#19
Maely P Fávero-Retto, Luiz Henrique Guerreiro, Cássio M Pessanha, Leonardo C Palmieri, Luís Maurício T R Lima
The characterization of conformational and oligomeric distribution of proteins is of paramount importance for the understanding of the correlation between structure and function. Among the bioanalytical approaches currently available, the electrospray ionization-mass spectrometry (ESI-MS) coupled to ion mobility spectrometry (IMS) is the best suited for high resolution identification with high sensitivity, allowing the in situ separation of oligomeric and conformational species. We tested the performance of the ESI-MS technique along with the IMS separation approach on a broad variety of insulin and insulin analogues with distinct oligomeric distribution pattern...
January 2017: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/28302541/trends-on-analytical-characterization-of-polysorbates-and-their-degradation-products-in-biopharmaceutical-formulations
#20
REVIEW
Ariadna Martos, Wendelin Koch, Wim Jiskoot, Klaus Wuchner, Gerhard Winter, Wolfgang Friess, Andrea Hawe
Among many other applications, polysorbates (PSs) are used as the most common surfactants in biopharmaceutical products in particular to protect proteins against interfacial stress. Structural heterogeneity, presence of degradants and other impurities, and tendency for degradation are interrelated features found in commercial PSs with a direct impact on their functional properties in biopharmaceutical products. These pose a challenge for the analytical characterization of PSs at different stages of product development...
July 2017: Journal of Pharmaceutical Sciences
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