Hydrophobic salts markedly diminish viscosity of concentrated protein solutions.

Abstract:

:Reducing viscosities of concentrated solutions of therapeutic proteins is important for their subcutaneous and intravenous delivery. Although inorganic salts and optimizing the pH were previously reported to dramatically lower the viscosity of a monoclonal antibody solution, herein we have determined these effects not to be general. Separately, we have found that hydrophobic ionic excipients, both anionic and cationic, substantially decrease the viscosity of concentrated (300-400 mg/mL) aqueous solutions of bovine serum albumin and γ-globulin. The more hydrophobic the excipient, the greater its viscosity-lowering effect is. With cationic ones, the concomitant contribution of the counter-ion broadly follows the chaotropic order. The most potent excipients lower the viscosity over fourfold to levels far below the 50 cP threshold for subcutaneous injections. The observed viscosity reductions are rationalized in terms of three-dimensional transient protein networks formed in concentrated solutions due to hydrophobic and, to a lesser extent, ionic interactions. These reversible protein aggregates are responsible for strong resistance to flow in concentrated protein solutions and hence their high viscosity; hydrophobic ions apparently effectively compete for these interprotein interactions, thereby giving rise to less viscous solutions.

journal_name

Biotechnol Bioeng

authors

Du W,Klibanov AM

doi

10.1002/bit.22983

subject

Has Abstract

pub_date

2011-03-01 00:00:00

pages

632-6

issue

3

eissn

0006-3592

issn

1097-0290

journal_volume

108

pub_type

杂志文章
  • Microbial degradation of quinoline: Kinetic studies with Comamonas acidovorans DSM 6426.

    abstract::The microbial degradation of quinoline by Comamonas acidovorans was studied in a laboratory scale stirred tank reactor. In continuous culture experiments using quinoline as a sole source of carbon and nitrogen, it was shown by means of mass balances that quinoline was converted completely to biomass, carbon dioxide, a...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260420506

    authors: Miethling R,Hecht V,Deckwer WD

    更新日期:1993-08-20 00:00:00

  • Dynamic simulator for anaerobic digestion processes.

    abstract::A transient, two-culture model simulating methane production from biomass has been developed. The simulator, based partially on the work by Andrews and McCarty, is capable of calculating the hydrolysis products of several common organic materials, accommodating various substrate feeding modes, and simulating the trans...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260240903

    authors: Kleinstreuer C,Poweigha T

    更新日期:1982-09-01 00:00:00

  • Small-scale and automatable high-throughput compositional analysis of biomass.

    abstract::Conventional wet chemistry methods to determine biomass composition are labor- and time-intensive and require larger amounts of biomass (300 mg) than is often available. To overcome these limitations and to support a high-throughput pretreatment and hydrolysis (HTPH) screening system, this article reports on the devel...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.22937

    authors: DeMartini JD,Studer MH,Wyman CE

    更新日期:2011-02-01 00:00:00

  • Trap and release of oligonucleotide using pH-responsive amphoteric particle prepared by interfacial polymerization in W/O miniemulsion system.

    abstract::Novel amphoteric particles are prepared by an interfacial polyaddition reaction of ethylene glycol diglycidyl ether (EGDGE) and L-lysine in a water-in-oil (W/O) miniemulsion system. The zeta-potential of the copolymer particle as a function of pH indicates a sigmoid curve with an isoelectric point at pH 8.7 due to the...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.20711

    authors: Taira S,Du YZ,Kodaka M

    更新日期:2006-02-05 00:00:00

  • Continuous acetone-butanol-ethanol (ABE) fermentation using immobilized cells of Clostridium acetobutylicum in a packed bed reactor and integration with product removal by pervaporation.

    abstract::An integrated solvent (ABE) fermentation and product removal process was investigated. A stable solvent productivity of 3.5 g/L h was achieved by using cells of Clostridium acetobutylicum immobilized onto a packed bed of bonechar, coupled with continuous product removal by pervaporation. Using a concentrated feed solu...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260380510

    authors: Friedl A,Qureshi N,Maddox IS

    更新日期:1991-08-20 00:00:00

  • Destruction and formation of toxins by one bacterial species affect biodegradation by a second species.

    abstract::Two strains of Pseudomonas able to grow on phenol or p-nitrophenol (PNP) were isolated from sewage. Pseudomonas sp. PN101 mineralized and formed nitrite from PNP but did not mineralize phenol, and Pseudomonas sp. PH111 mineralized phenol but not PNP. Phenol increased the lag period before Pseudomonas sp. PN101 grew on...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260330706

    authors: Murakami Y,Alexander M

    更新日期:1989-02-20 00:00:00

  • Physiologic mechanisms of sequential products synthesis in 1,3-propanediol fed-batch fermentation by Klebsiella pneumoniae.

    abstract::The glycerol fed-batch fermentation by Klebsiella pneumoniae CGMCC 1.6366 exhibited the sequential synthesis of products, including acetate, 1,3-propanediol (1,3-PD), 2,3-butanediol, ethanol, succinate, and lactate. The dominant flux distribution was shifted from acetate formation to 1,3-PD formation in early- exponen...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.21830

    authors: Zheng ZM,Xu YZ,Liu HJ,Guo NN,Cai ZZ,Liu DH

    更新日期:2008-08-01 00:00:00

  • Elimination of hydrophobic volatile organic compounds in fungal biofilters: reducing start-up time using different carbon sources.

    abstract::Fungal biofilters have been recently studied as an alternative to the bacterial systems for the elimination of hydrophobic volatile organic compounds (VOC). Fungi foster reduced transport limitation of hydrophobic VOCs due to their hydrophobic surface and extended gas exchange area associated to the hyphal growth. Nev...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.23003

    authors: Vergara-Fernández A,Hernández S,Revah S

    更新日期:2011-04-01 00:00:00

  • Measuring enzyme motility in organic media using novel H-D exchange methodology.

    abstract::A novel deuterium ((2)H) NMR technique as developed for measuring the total number of deuterons exchanged by lyophilised protein samples following hydrogen-deuterium (H-D) exchange. Using this methodology differences in the H-D exchange behaviour of the proteolytic enzyme subtilisin Carlsberg hydrated either in air or...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:

    authors: Hutcheon GA,Parker MC,Moore BD

    更新日期:2000-11-05 00:00:00

  • Modeling biocide action against biofilms.

    abstract::A phenomenological model of biocide action against microbial biofilms was derived. Processes incorporated in the model include bulk flow in and out of a well-mixed reactor, transport of dissolved species into the biofilm, substrate consumption by bacterial metabolism, bacterial growth, advection of cell mass within th...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/(SICI)1097-0290(19960220)49:4<445::AID-BIT

    authors: Stewart PS,Hamilton MA,Goldstein BR,Schneider BT

    更新日期:1996-02-20 00:00:00

  • Gas sensing in microplates with optodes: influence of oxygen exchange between sample, air, and plate material.

    abstract::Microplates with integrated optical oxygen sensors are a new tool to study metabolic rates and enzyme activities. Precise measurements are possible only if oxygen exchange between the sample and the environment is known. In this study we quantify gas exchange in plastic microplates. Dissolved oxygen was detected using...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.20348

    authors: Arain S,Weiss S,Heinzle E,John GT,Krause C,Klimant I

    更新日期:2005-05-05 00:00:00

  • Extension of cell membrane boosting squalene production in the engineered Escherichia coli.

    abstract::Squalene is a lipophilic and non-volatile triterpene with many industrial applications for food, pharmaceuticals, and cosmetics. Metabolic engineering focused on optimization of the production pathway suffer from little success in improving titers because of a limited space of the cell membrane accommodating the lipop...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.27511

    authors: Meng Y,Shao X,Wang Y,Li Y,Zheng X,Wei G,Kim SW,Wang C

    更新日期:2020-07-21 00:00:00

  • Trichloroethene and cis-1,2-dichloroethene concentration-dependent toxicity model simulates anaerobic dechlorination at high concentrations. II: continuous flow and attached growth reactors.

    abstract::A model that was used to describe toxicity from high concentrations of chlorinated aliphatic hydrocarbons (CAHs) on reductively dechlorinating cultures in batch reactors (Sabalowsky and Semprini (in press)) was extended here to simulate observations in continuous flow suspended and attached growth reactors. The reduct...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.22822

    authors: Sabalowsky AR,Semprini L

    更新日期:2010-10-15 00:00:00

  • Neurogenesis and neuronal communication on micropatterned neurochips.

    abstract::Neural networks are formed by accurate connectivity of neurons and glial cells in the brain. These networks employ a three-dimensional bio-surface that both assigns precise coordinates to cells during development and facilitates their connectivity and functionality throughout life. Using specific topographic and chemi...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.20618

    authors: Bani-Yaghoub M,Tremblay R,Voicu R,Mealing G,Monette R,Py C,Faid K,Sikorska M

    更新日期:2005-11-05 00:00:00

  • Fluorescent detection of cyanobacterial DNA using bacterial magnetic particles on a MAG-microarray.

    abstract::Bacterial magnetic particles (BMPs) were used for the identification of cyanobacterial DNA. Genus-specific oligonucleotide probes for the detection of Anabaena spp., Microcystis spp., Nostoc spp., Oscillatoria spp., and Synechococcus spp. were designed from the variable region of the cyanobacterial 16S rDNA of 148 str...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.1073

    authors: Matsunaga T,Nakayama H,Okochi M,Takeyama H

    更新日期:2001-06-05 00:00:00

  • Anaerobic methanethiol degradation and methanogenic community analysis in an alkaline (pH 10) biological process for liquefied petroleum gas desulfurization.

    abstract::Anaerobic methanethiol (MT) degradation by mesophilic (30 degrees C) alkaliphilic (pH 10) communities was studied in a lab-scale Upflow Anaerobic Sludge Bed (UASB) reactor inoculated with a mixture of sediments from the Wadden Sea (The Netherlands), Soap Lake (Central Washington), and Russian soda lakes. MT degradatio...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.21933

    authors: van Leerdam RC,Bonilla-Salinas M,de Bok FA,Bruning H,Lens PN,Stams AJ,Janssen AJ

    更新日期:2008-11-01 00:00:00

  • Hydrodynamic characteristics of immobilized cell beads in a liquid-solid fluidized-bed bioreactor.

    abstract::This study examined the hydrodynamic characteristics of a liquid-solid fluidized-bed bioreactor using elastic particles (PVA gel beads) of various diameters as carriers. The drag coefficient-Reynolds number, velocity-voidage, and expansion index-Reynolds number relationships observed during fluidization of PVA gel bea...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.10710

    authors: Wu JY,Chen KC,Chen CT,Hwang SC

    更新日期:2003-09-05 00:00:00

  • Optimized release of recombinant proteins by ultrasonication of E. coli cells.

    abstract::The release kinetics of beta-galactosidase protein have been determined during small-scale ultrasonication of E. coli cells. Among several studied parameters, ionic strength and cell concentration have the least influence on the rate of protein recovery, whereas sample volume and acoustic power dramatically affect the...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0290(19980605)58:5<536::aid-bit

    authors: Feliu JX,Cubarsi R,Villaverde A

    更新日期:1998-06-05 00:00:00

  • Active-site titration of serine proteases in organic solvents.

    abstract::Calculation of kinetic constants of an enzymatic reaction in organic solvents requires knowledge of the functional active-site concentration in organic solvents, and this can be significantly different than that in water. An experimental method for active-site titration of serine proteases in organic media has been de...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/(SICI)1097-0290(19960505)50:3<329::AID-BIT

    authors: Wangikar PP,Carmichael D,Clark DS,Dordick JS

    更新日期:1996-05-05 00:00:00

  • Removal and upgrading of lignocellulosic fermentation inhibitors by in situ biocatalysis and liquid-liquid extraction.

    abstract::Hydroxycinnamic acids are known to inhibit microbial growth during fermentation of lignocellulosic biomass hydrolysates, and the ability to diminish hydroxycinnamic acid toxicity would allow for more effective biological conversion of biomass to fuels and other value-added products. In this work, we provide a proof-of...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.25473

    authors: Tomek KJ,Saldarriaga CR,Velasquez FP,Liu T,Hodge DB,Whitehead TA

    更新日期:2015-03-01 00:00:00

  • Modeling brewers' yeast flocculation

    abstract::Flocculation of yeast cells occurs during the fermentation of beer. Partway through the fermentation the cells become flocculent and start to form flocs. If the environmental conditions, such as medium composition and fluid velocities in the tank, are optimal, the flocs will grow in size large enough to settle. After ...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0290(19980205)57:3<330::aid-bit

    authors: van Hamersveld EH,van der Lans RG,Caulet PJ,Luyben KC

    更新日期:1998-02-05 00:00:00

  • Algal productivity modeling: a step toward accurate assessments of full-scale algal cultivation.

    abstract::A new biomass productivity model was parameterized for Chlorella vulgaris using short-term (<30 min) oxygen productivities from algal microcosms exposed to 6 light intensities (20-420 W/m(2)) and 6 temperatures (5-42 °C). The model was then validated against experimental biomass productivities recorded in bench-scale ...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.25517

    authors: Béchet Q,Chambonnière P,Shilton A,Guizard G,Guieysse B

    更新日期:2015-05-01 00:00:00

  • Shikimic acid production by a modified strain of E. coli (W3110.shik1) under phosphate-limited and carbon-limited conditions.

    abstract::Shikimic acid is one of several industrially interesting chiral starting materials formed in the aromatic amino acid pathway of plants and microorganisms. In this study, the physiology of a shikimic acid producing strain of Escherichia coli (derived from W3110) deleted in aroL (shikimic acid kinase II gene), was compa...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.20546

    authors: Johansson L,Lindskog A,Silfversparre G,Cimander C,Nielsen KF,Lidén G

    更新日期:2005-12-05 00:00:00

  • Permeability of a growing biofilm in a porous media fluid flow analyzed by magnetic resonance displacement-relaxation correlations.

    abstract::Biofilm growth in porous media is difficult to study non-invasively due to the opaqueness and heterogeneity of the systems. Magnetic resonance is utilized to non-invasively study water dynamics within porous media. Displacement-relaxation correlation experiments were performed on fluid flow during biofilm growth in a ...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.24803

    authors: Vogt SJ,Sanderlin AB,Seymour JD,Codd SL

    更新日期:2013-05-01 00:00:00

  • Saccharification of bamboo carbohydrates for the production of ethanol.

    abstract::Bamboo carbohydrates were hydrolyzed with commercial amylases and a mixture of fungal culture broths containing cellulolytic and hemicellulolytic enzymes. The effects of cooking temperature and the size of fiber particles were also investigated. It was found that the higher the cooking temperature, the higher the rate...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260250415

    authors: De Menezes TJ,Dos Santos CL,Azzini A

    更新日期:1983-04-01 00:00:00

  • Enzymatic transformations in supersaturated substrate solutions: I. A general study with glycosidases.

    abstract::The results of an initial study of enzymatic catalysis in metastable supersaturated solutions of carbohydrates are presented. It has been shown that such solutions, formed in the presence of small amounts of water and alcohol as plasticizers, are sufficiently stable under ambient conditions to enable enzymatic transfo...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:

    authors: Millqvist-Fureby A,Gill IS,Vulfson EN

    更新日期:1998-10-20 00:00:00

  • Escherichia coil growth dynamics: A three-pool biochemically based description.

    abstract::A three-pool growth model of an individual Escherichia coli cell is described herein. The model is based on a previously developed chemically structured complex single cell growth model. The reduction in model complexity and the identification of the essential modes of motion, over the time scale of growth, is achieve...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.260310203

    authors: Joshi A,Palsson BO

    更新日期:1988-02-05 00:00:00

  • A mechanistic model of the enzymatic hydrolysis of cellulose.

    abstract::A detailed mechanistic model of enzymatic cellulose hydrolysis has been developed. The behavior of individual cellulase enzymes and parameters describing the cellulose surface properties are included. Results obtained for individual enzymes (T. reesei endoglucanase 2 and cellobiohydrolase I) and systems with both enzy...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.22789

    authors: Levine SE,Fox JM,Blanch HW,Clark DS

    更新日期:2010-09-01 00:00:00

  • Fabricating PLGA microparticles with high loads of the small molecule antioxidant N-acetylcysteine that rescue oligodendrocyte progenitor cells from oxidative stress.

    abstract::Reactive oxygen species (ROS), encompassing all oxygen radical or non-radical oxidizing agents, play key roles in disease progression. Controlled delivery of antioxidants is therapeutically relevant in such oxidant-stressed environments. Encapsulating small hydrophilic molecules into hydrophobic polymer microparticles...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.26443

    authors: Murphy NP,Lampe KJ

    更新日期:2018-01-01 00:00:00

  • Coping with inadvertent lysis of Escherichia coli cultures: Strains resistant to lysogeny and infection by the stealthy lysogenic phage Φ80.

    abstract::Phage Φ80 can infect Escherichia coli in a stealthy manner and persist by forming lysogens. Such Φ80 lysogens are fairly common and often go undetected unless the host is grown at temperatures below 37°C. Since low growth temperatures are required for growing temperature-sensitive mutants and often preferred for large...

    journal_title:Biotechnology and bioengineering

    pub_type: 杂志文章

    doi:10.1002/bit.26971

    authors: Srinivas S,Cronan JE

    更新日期:2019-07-01 00:00:00