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Imaging and size measurement of nanoparticles in aqueous medium by use of atomic force microscopy


Size control of nanoparticles in nanotechnology-based drug products is crucial for their successful development, since the in vivo pharmacokinetics of nanoparticles are size-dependent. In this study, we evaluated the use of atomic force microscopy (AFM) for imaging and size measurement of nanoparticles in aqueous medium. The height sizes of rigid polystyrene nanoparticles and soft liposomes were measured by AFM and were compared with the hydrodynamic sizes measured by dynamic light scattering (DLS). The lipid compositions of the studied liposomes were similar to those of commercial products. AFM proved to be a viable method for obtaining images of both polystyrene nanoparticles and liposomes in aqueous medium. For the polystyrene nanoparticles, the average height size observed by AFM was similar to the average number-weighted diameter obtained by DLS, indicating the usefulness of AFM for measuring the sizes of nanoparticles in aqueous medium. For the liposomes, the height sizes obtained by AFM differed depending upon the procedures of immobilizing the liposomes onto a solid substrate. In addition, the resultant average height sizes of the liposomes were smaller than those obtained by DLS. This knowledge will help the correct use of AFM as a powerful tool for imaging and size measurement of nanotechnology-based drug products for clinical use.

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This work was supported in part by the Research on Development of New Drugs and Research on Regulatory Harmonization and Evaluation of Pharmaceuticals, Medical Devices, Regenerative and Cellular Therapy Products, Gene Therapy Products, and Cosmetics from the Japan Agency for Medical Research and Development, AMED.

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Correspondence to Kumiko Sakai-Kato.

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Takechi-Haraya, Y., Goda, Y. & Sakai-Kato, K. Imaging and size measurement of nanoparticles in aqueous medium by use of atomic force microscopy. Anal Bioanal Chem 410, 1525–1531 (2018).

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  • Atomic force microscopy
  • Dynamic light scattering
  • Size measurement
  • Polystyrene nanoparticle
  • Liposome