The utility of asymmetric flow field-flow fractionation for preclinical characterization of nanomedicines
Abstract
Dynamic light scattering (DLS), transmission electron microscopy (TEM), and reversed phase-high performance liquid chromatography (RP-HPLC) are staples of nanoparticle characterization for size distribution, shape/morphology, and composition, respectively. These techniques are simple and provide important details on sample characteristics. However, DLS and TEM are routinely done in batch-mode, while RP-HPLC affords separation of components within the entire sample population, regardless of sample polydispersity. While batch-mode analysis is informative and should be a first-step analysis for any material, it may not be ideal for polydisperse formulations, such as many nanomedicines. Herein, we describe the utility of asymmetric flow field-flow fractionation (AF4) as a useful tool for a more thorough understanding of these inherently polydisperse materials. AF4 was coupled with in-line DLS for an enhanced separation and resolution of various size populations in a nanomaterial. Additionally, the various size populations were collected for offline analysis by TEM for an assessment of different shape populations, or RP-HPLC to provide a compositional analysis of each individual size population. This technique was also extended to assess nanoparticle stability, i.e., drug release, both in buffer and physiologically relevant matrix, as well as qualitatively evaluate the protein binding capacity of nanomedicines. Overall, AF4 is proven to be a very versatile technique and can provide a wealth of information on a material's polydispersity and stability. Moreover, the ability to conduct analysis in physiological matrices provides an advantage that many other routine analytical techniques do not. Graphical Abstract.
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Ghezzi, M., Pescina, S., Padula, C., Santi, P., Del Favero, E., Cantù, L., & Nicoli, S. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.02.031 · Cited by 1,135 · see citing works
- Authors
- Hu, Y., Crist, R. M., & Clogston, J. D.
- Affiliations
- Frederick National Laboratory for Cancer Research (US)
- Corresponding author
- Clogston, Jeffrey D.
- Venue
- Analytical and Bioanalytical Chemistry
- Published
- 2019-11-27
- Volume
- 412
- Issue
- 2
- Pages
- 425-438
- ISSN
- 1618-2642 (ISSN-L)
- 1618-2650
- OpenAlex
- W2991326193
- Cited by
- 49
- References
- 37
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 11 · 2023: 6 · 2022: 5 · 2021: 12 · 2020: 6
- FWCI
- 3.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Analytical and Bioanalytical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute, National Institutes of Health (Contract No. HHSN261200800001E)
- Topics
- Physical Sciences › Engineering › Computational Mechanics › Field-Flow Fractionation Techniques
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Keywords
- asymmetrical flow field-flow fractionation, polydispersity, nanoparticle size distribution, nanoparticle morphology, nanoparticle composition, nanoparticle stability, drug release, protein binding, transmission electron microscopy, reversed-phase HPLC
- MeSH terms
- Dynamic Light Scattering, Chromatography, High Pressure Liquid, Humans, Fractionation, Field Flow, Microscopy, Electron, Transmission, Nanomedicine, Nanoparticles, Chromatography, Reverse-Phase
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