A Taylor dispersion analysis method for the sizing of therapeutic proteins and their aggregates using nanolitre sample quantities

Hulse, Wendy L.; Forbes, Robert T.

doi:10.1016/j.ijpharm.2011.06.045

Cited by 37 publications

(35 citation statements)

References 22 publications

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“…This is attributed to the different synthesis route, where the concentration of Larginine as catalyst has a strong influence on the polydispersity [27]. We have used BSA throughout our study, since it has previously been used as proof-of-concept for TDA [9][10][11]. As can be expected, no adequate TEM micrograph could be obtained for BSA due to insufficient contrast.…”

Section: Introductionmentioning

confidence: 99%

“…proteincrowded suspensions, high particle concentration etc.) or samples where only limited sample preparation is possible [9][10][11]. There are possibilities to overcome some of these problems, for example by the use of depolarized dynamic light scattering, as described by Balog et al [12].…”

Section: Introductionmentioning

confidence: 99%

“…In other words, larger NPs will be dispersed more strongly by convection than smaller ones, and by detecting the band broadening of these concentration fronts, and obtaining so-called Taylorgrams of the NPs, one can determine hydrodynamic sizes by fitting the Taylorgram against a Gaussian function [13][14][15]. In the past, TDA has mainly been used to observe chemical reactions [16,17], or to determine the diffusion coefficient of small molecules, proteins, and polymers [10,11,[18][19][20]. With the increasing interest in nanomaterials, some work has been done in the past [9,13,15,18,[21][22][23][24] to investigate whether TDA can be used for NP characterization.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, the method is not only limited to spherical NPs but can be applied to other shapes, such as rods [18]. However, research focused on NP characterization with TDA has been focused on polymeric samples with a limited number of samples and few different sizes [9][10][11]18,25]. Due to the scope of this manuscript we opted to compile a list of additional literature concerning Taylor Dispersion and nanoparticle analysis and add it to the supplementary information rather than continue here.…”

Section: Introductionmentioning

confidence: 99%

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Taylor Dispersion of Inorganic Nanoparticles and Comparison to Dynamic Light Scattering and Transmission Electron Microscopy

Urban

Milošević

Bossert

et al. 2018

Colloid and Interface Science Communications

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A B S T R A C TTaylor dispersion analysis (TDA) is an analytical method that has so far mainly been utilized to determine the diffusion coefficient of small molecules, and proteins. Due to increasing interest in nanoscience, some research has been done on the applicability of TDA towards characterizing nanoparticles. This work aims to expand this knowledge and give insight into the range for which TDA can be used for nanoparticle characterization, focusing on various materials and sizes. The TDA setup shown in this work was successful in characterizing all engineered metallic, non-metallic nanoparticles, and proteins tested in this work. Results were compared to dynamic light scattering and electron microscopy, and were in good agreement with both methods. Taking into consideration the wide range of nanoparticle sizes that can be characterized, the minimal sample preparation, and sample volume, required and the simplicity of the method, TDA can be considered as a valuable technique for nanoparticle characterization.When looking at the huge array of properties that nanoparticles (NPs) possess, it is not surprising that they have found their way into a multitude of scientific research areas, and industrial applications [1]. Interesting NP phenomena are mostly governed by their size, and for many applications it is imperative that the NPs not only have a very specific size but also display a narrow particle size distribution [2]. For example, the heating properties of superparamagnetic iron oxide nanoparticles (SPIONs), which are being investigated as mediators of hyperthermia in cancer treatment, are dependent on their size and size distribution. Therefore, the characterization of nanoparticle size is crucial to ensure their functionality [3]. For this purpose, several analytical methods such as dynamic light scattering (DLS), NP tracking analysis (NTA), UV-Vis spectroscopy, field-flow fractionation, analytical ultracentrifugation, and transmission electron microscopy (TEM) have been utilized to characterize NP sizes and size distributions [4][5][6][7][8]. Each method has its advantages and disadvantages, and a combination of techniques is typically recommended to adequately characterize NPs [4]. For example, TEM provides information about NP core sizes, but cannot evaluate NP hydrodynamic diameters. Conversely, DLS and NTA can evaluate particle hydrodynamic diameter and colloidal stability, but are limited by the quality of light scattering and require a deeper knowledge of the theory and model-fitting to properly analyze the raw data. With scattering-based techniques, the limit of detection for NPs depends on the sensitivity of the detection of scattered light, and factors such as the material refractive index, particle size, shape and the wavelength used for detection. Furthermore, standard DLS measurements struggle with analyzing NPs in complex environments (e.g. proteincrowded suspensions, high particle concentration etc.) or samples where only limited sample preparation is possible [9][10][11]. There are pos...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Taylor Dispersion of Inorganic Nanoparticles and Comparison to Dynamic Light Scattering and Transmission Electron Microscopy

Urban

Milošević

Bossert

et al. 2018

Colloid and Interface Science Communications

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show abstract

“…An instrument utilizing UV imaging detection at two windows for samples flowing through a capillary has been developed specifically for TDA and complementary solution viscosity measurements, and applied for characterising proteins and their formulations (Hawe et al, 2011;Forbes, 2011a, 2011b). Very high precision (RSD < 1%) is obtained in protein sizing (Paraytec, 2010;Hulse and Forbes 2011b;Hulse et al, 2013). Use of methodology with two windows has the benefit that contributions to variance other than Taylor dispersion, e.g.…”

Section: Introductionmentioning

confidence: 99%

Characterisation of aggregates of cyclodextrin-drug complexes using Taylor Dispersion Analysis

Zaman

Bright

Adams

et al. 2017

International Journal of Pharmaceutics

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There is a need to understand the nature of aggregation of cyclodextrins (CDs) with guest molecules in increasingly complex formulation systems. To this end an innovative application of Taylor dispersion analysis (TDA) and comparison with dynamic light scattering (DLS) have been carried out to probe the nature of ICT01-2588 (ICT-2588), a novel tumor-targeted vascular disrupting agent, in solvents including a potential buffered formulation containing 10% hydroxypropyl-betacyclodextrin. The two hydrodynamic sizing techniques give measurement responses are that fundamentally different for aggregated solutions containing the target molecule, and the benefits of using TDA in conjunction with DLS are that systems are characterised through measurement of both mass-and z-average hydrodynamic radii. Whereas DLS measurements primarily resolve the large aggregates of ICT01-2588 in its formulation medium, methodology for TDA is described to determine the size and notably to quantify the proportion of monomers in the presence of large aggregates, and at the same time measure the formulation viscosity. Interestingly TDA and DLS have also distinguished between aggregate profiles formed using HP-beta-CD samples from different suppliers. The approach is expected to be widely applicable to this important class of drug formulations where drug solubility is enhanced by cyclodextrin and other excipients. To: The Editor, International Journal of Pharmaceutics From: Rob Forbes and David GoodallWe have revised the manuscript to reflect the amendments of the reviewers. The original cover letter is below.We are submitting this article, which describes novel work showing benefits of use of Taylor dispersion analysis in conjunction with dynamic light scattering to characterize ICT01-2588, a tumour-targeted vascular disrupting agent, in a potential formulation medium containing 10% hydroxypropyl--cyclodextrin as a solubility enhancing agent. Our approach is expected to be widely applicable to this important class of drug formulations where drug solubility is enhanced by cyclodextrin and other excipients, and is a contribution to advancing an understanding of the nature of self-assembly in such complex systems.The lead reviwer suggested is Thorsteinn Loftsson, who is a member of your Editorial Advisory Board. We cite a number of his papers. Of the other suggested referees. We cite work on Taylor dispersion analysis by the other two proposed referees, Ana Ribeiro and Jesper Ostergaard, and Robert HoylstPlease note that if possible we would like to name two corresponding authors, Robert T. Forbes (lead corresponding author) and David M. Goodall (second corresponding author). If this is not possible, it should be just Robert T. Forbes. The bulk of this work was conducted whilst Professor Forbes was at the University of Bradford, which is listed as his affiliation #1. He is currently at the University of Central Lancashire, which is listed as affiliation #2.Regarding declaration of conflict of interest guidelines, please note the foll...

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Latest Insights and Methods in Analyzing Liquid Dense Clusters and Crystal Nucleation

Brognaro

Betzel

2018

Encyclopedia of Analytical Chemistry

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Liquid dense clusters (LDCs) are distinct membrane‐less microcompartments of molecules in aqueous solution, which arise in the process of liquid–liquid phase separation. LDC formation is observed most frequently in vivo during cell development, in neurodegenerative diseases and stress signaling, as well as in vitro, in liquid–solid phase transition. LDCs emerge spaciotemporally depending on the physicochemical environment, surface properties, and conformational flexibility of the molecules involved. Knowledge about structural and dynamic properties of growth and division of different macromolecule LDCs and other clustering phenomena, such as gels and fibers, is till now incomplete and only simplified thermodynamic models are available to predict some aspects of clustering so far. For example, for crystal growth a multistep mechanism is today most commonly accepted, starting with the early formation of LDCs, followed by a self‐organization within this LDCs and initial nucleation of an ordered crystal lattice. Therefore, insights about the LDCs formation and stability will also support directed optimization of macromolecule crystallization and will shed light on physiological LDC processes as well. Furthermore, it will support the establishment of new sample preparation and imaging techniques in structural biology utilizing latest and upcoming X‐ray imaging methods at high‐intensity radiation sources.

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A Taylor dispersion analysis method for the sizing of therapeutic proteins and their aggregates using nanolitre sample quantities

Cited by 37 publications

References 22 publications

Taylor Dispersion of Inorganic Nanoparticles and Comparison to Dynamic Light Scattering and Transmission Electron Microscopy

Taylor Dispersion of Inorganic Nanoparticles and Comparison to Dynamic Light Scattering and Transmission Electron Microscopy

Characterisation of aggregates of cyclodextrin-drug complexes using Taylor Dispersion Analysis

Latest Insights and Methods in Analyzing Liquid Dense Clusters and Crystal Nucleation

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