Nanoparticle formulation modalities: applying light scattering to screening and characterization

Daniel Some, Wyatt Technology Corp., Santa Barbara, CA, USA (dsome@wyatt.com)

From traditional small molecule drugs to vaccines, gene vectors and personalized medicine, nanoparticle modalities are increasingly of interest for enhanced and safe delivery. Characterization and quality control among the most important missions of developing any therapeutic, and particularly challenging for complex nanoparticles. 

While light scattering is well known in nanoparticle research, traditional technologies such as dynamic and electrophoretic light scattering typically do not provide the level of detail needed for full characterization. Likewise they do not offer the degree of automation and throughput required to quickly bring a new nanoparticle formulation to pre-clinical and clinical trials, and then rapidly scale up the process to full production and quality control. This presentation explores three light-scattering-based technologies that overcome these hurdles: high-throughput dynamic light scattering (HT-DLS), fully-automated electrophoretic light scattering (A-ELS), and online light scattering coupled to asymmetric-flow field-flow fractionation (AF4-MALS).

A-ELS, and HT-DLS in particular, provide the usual information on colloidal size, aggregation and zeta potential familiar from traditional technologies, but enable implementation of matrix testing for formulation and process development that would not be feasible with a non-automated instrument. Several examples will be discussed, ranging from initial development phases to process optimization.

AF4-MALS is an extremely powerful tool for macromolecular and nanoparticle characterization. It combines size-based separation with detailed structural and compositional data for each size fraction. Size, shape, structure, concentration and zeta potential are determined by onlne light scattering. Composition, including encapsulation, is determined from online spectroscopy combined with light scattering as well as mass spectrometry.  Fractions may be collected for further study. Examples presented include VLP-based gene vectors, liposome- and polymersome-based drug carriers. 

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Abstract Reference & Short Personal Biography of Presenting Author

Daniel Some is Principal Scientist at Wyatt Technology Corporation, where he explores new applications of light scattering for characterization of macromolecules and nanoparticles, in particular for the life sciences and pharmaceutical industries. He developed Wyatt's Calypso composition-gradient multi-angle light scattering (CG-MALS) system for label-free, in-solution characterization of protein-protein, protein-DNA and other macromolecular interactions. Dr. Some is a graduate of the Technion - Israel Institute of Technology, and obtained his PhD at Brown University, both in the Physics Department. He has carried out postdoctoral research at Los Alamos National Laboratory and the Weizmann Institute of Science.