Abstract
As the physicochemical properties of drug delivery systems are governed not only by the material properties which they are compose of but by their size that they conform, it is crucial to determine the size and distribution of such systems with nanometer-scale precision. The standard technique used to measure the size distribution of nanometer-sized particles in suspension is dynamic light scattering (DLS). Recently, nanoparticle tracking analysis (NTA) has been introduced to measure the diffusion coefficient of particles in a sample to determine their size distribution in relation to DLS results. Because DLS and NTA use identical physical characteristics to determine particle size but differ in the weighting of the distribution, NTA can be a good verification tool for DLS and vice versa. In this study, we evaluated two NTA data analysis methods based on maximum-likelihood estimation, namely finite track length adjustment (FTLA) and an iterative method, on monodisperse polystyrene beads and polydisperse vesicles by comparing the results with DLS. The NTA results from both methods agreed well with the mean size and relative variance values from DLS for monodisperse polystyrene standards. However, for the lipid vesicles prepared in various polydispersity conditions, the iterative method resulted in a better match with DLS than the FTLA method. Further, it was found that it is better to compare the native number-weighted NTA distribution with DLS, rather than its converted distribution weighted by intensity, as the variance of the converted NTA distribution deviates significantly from the DLS results.
Highlights
In the analysis of macromolecular assemblies, various techniques are used to measure the physical properties of samples, including imaging[30,31], separation of particles[32,33], scattered light[34,35] and those measurements are related to the size by conversions relying on various physical principles[36]
This paper introduces and compares two particle size measurement techniques, dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA), for the size characterization of polydisperse macromolecular assemblies
While both techniques acquire size information by detecting the diffusion coefficient of the measured particles, they differ in the quantity of the size distribution they report, with NTA reporting number and DLS reporting intensity
Summary
In the analysis of macromolecular assemblies, various techniques are used to measure the physical properties of samples, including imaging[30,31], separation of particles[32,33], scattered light[34,35] and those measurements are related to the size by conversions relying on various physical principles[36]. Throughput is limited and limited sampling may result in biased information[36] Another strategy is to separate the particles in the sample, creating a spatial macromolecular redistribution in a medium, in which the degree of separation is determined by the mass or volume of the macromolecules and can be converted into their size[36]. Whereas DLS reads the intensity change of scattered light to find the diffusion coefficient of particles, NTA calculates the diffusion coefficient based on the movements of individual particles in successive optical video images[51,52] This difference in the detection principles of DLS and NTA results in a difference in the way that they report size, i.e., the quantities of the particles measured by DLS and NTA are weighted by intensity and number, respectively, which makes NTA an excellent technique for verifying DLS results. When the comparison was extended to polydisperse samples such as proteins and vesicles[52,54,55,56], the results showed better size resolution in NTA compared with DLS
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