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Liposomes are nowadays frequently used as drug delivery systems, and as such requires that they are well characterized for manufacturing and batch release. This characterization includes their size and size distribution. For these parameters, dynamic light scattering (DLS) is commonly used to characterize size and size distribution and also nanoparticle tracking analysis (NTA) has previously been shown to be useful for measuring liposomes size and concentration.1 This application note will demonstrate how the multi-angle DLS (MADLS®) based particle concentration measurement in the Zetasizer Ultra is capable of measuring the particle concentration as well as size and size distribution of a range of dilutions of a liposome sample. A comparison will be made with NTA measurements of the same samples.

Products:

NanoSight NS300

Date:

May 18 2018

Language:

English

Dynamic Light Scattering (DLS) is a powerful and sensitive technique for characterizing particles or macromolecules in dispersion, due to its ability to resolve particle or molecular sizes ranging from sub nanometer to several microns. This sensitivity also means that DLS is a useful technique to characterize aggregated material, which may occur in far smaller quantities but is of a significant importance in many applications. Typically, however, the presence or dust (including filter spoil, column shedding, tracer aggregates or material from dirty lab ware), can have detrimental effects on the measurement of smaller sized particles and algorithms exist to suppress these effects. In this application note we present a new approach to handling DLS data which prevents the skewing of data for small particles whilst retaining insight into the presence of aggregates that may otherwise be lost, whereby the relative abundance and size of aggregates can be deduced. .

Dynamic light scattering has been vastly explored as a tool for micelles characterization, not only for their size and stability, but also to determine the critical micellization concentration (CMC) and temperature (CMT)1-3. As a result of the unimers aggregation, as a function of the temperature for the case of this study, an increase in the scattered intensity is expected due to larger particles scattering substantially more photons. It’s been reported that for light-scattering techniques to be used reliably as CMC or CMT determination techniques, long correlation times are needed 1,4,5 which make this time-consuming and hence it’s not usually considered as a primary technique. We suggest in this application note, that DLS can be used in conjugation with other techniques to determine the CMT in a highly reproducible and time-efficient manner.

Dynamic Light Scattering (DLS) allows the hydrodynamic size of particles in dispersion to be measured by quantifying their diffusive motion. At particle sizes approaching the upper size range for DLS, sedimentation, thermal currents and number fluctuations can mean that the detected scattering no longer accurately describes purely diffusive motion, and particle size analysis becomes less accurate. Here we will discuss how the Low Volume Disposable Sizing Cell can improve data quality at large particle sizes and allow the entire size range of DLS to be explored without modification of the dispersant system.

When producing particles of a known size, the monodispersity of the samples in terms of both size and shape is important and often requires a high-resolution technique such as TEM to look at these sample properties. For example, Particle Works, a brand of Blacktrace Holdings Ltd, produce gold nanoparticles which must be highly monodisperse and have high batch-to-batch consistency, with CV values as low as 5% for the size distribution and 2.5% for the batch consistency. Currently, Particle Works use TEM as the primary technique for characterizing their samples for QC. However, TEM is a time consuming and expensive technique that requires an experienced user to perform analysis. In this study we show how the Zetasizer Ultra can be used to identify the majority of 'out of specification' batches of gold nanoparticles and therefore significantly reduce the amount of TEM analysis required..