Multimodal Dispersion of Nanoparticles: A Comprehensive Evaluation of Size Distribution with 9 Size Measurement Methods

ABSTRACT

Purpose

Evaluation of particle size distribution (PSD) of multimodal dispersion of nanoparticles is a difficult task due to inherent limitations of size measurement methods. The present work reports the evaluation of PSD of a dispersion of poly(isobutylcyanoacrylate) nanoparticles decorated with dextran known as multimodal and developed as nanomedecine.

Methods

The nine methods used were classified as batch particle i.e. Static Light Scattering (SLS) and Dynamic Light Scattering (DLS), single particle i.e. Electron Microscopy (EM), Atomic Force Microscopy (AFM), Tunable Resistive Pulse Sensing (TRPS) and Nanoparticle Tracking Analysis (NTA) and separative particle i.e. Asymmetrical Flow Field-Flow Fractionation coupled with DLS (AsFlFFF) size measurement methods.

Results

The multimodal dispersion was identified using AFM, TRPS and NTA and results were consistent with those provided with the method based on a separation step prior to on-line size measurements. None of the light scattering batch methods could reveal the complexity of the PSD of the dispersion.

Conclusions

Difference between PSD obtained from all size measurement methods tested suggested that study of the PSD of multimodal dispersion required to analyze samples by at least one of the single size particle measurement method or a method that uses a separation step prior PSD measurement.

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Abbreviations

AFM:

Atomic force microscopy

AsFlFFF:

Asymmetrical flow field-flow fractionation

DCS:

Differential centrifugal sedimentation

DLS:

Dynamic light scattering

EM:

Electron microscopy

IBCA:

Isobutylcyanoacrylate

NTA:

Nanoparticle tracking analysis

PCCS:

Photon cross-correlation spectroscopy

PIBCA:

Poly(isobutylcyanoacrylate)

PSD:

Particle size distribution

PTA:

Particle tracking analysis

Qels:

Quasi elastic light scattering

SdFFF:

Sedimentation field-flow fractionation

SEM:

Scanning electron microscopy

SLS:

Static light scattering

TEM:

Transmission electron microscopy

TRPS:

Tunable resistive pulse sensing

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ACKNOWLEDGMENTS AND DISCLOSURES

This work was supported by BpI France (Project NICE). The authors acknowledge the Région Ile-de-France (“Equipement mi-lourd 2012” program, DIM Malinf) and the JPK Company for their active support. The authors acknowledge all persons who performed measurement with different instruments: Camille Roesch (Izon Science Europe Ltd, Magdalen Centre, The Oxford Science Park, Oxford, UK), Pierre Peotta (Malvern, Parc club de l’Université, Orsay, France), Philippe Violle (Sympatec, Orsay, France), Serge Réteaud (Beckman Coulter, Villepinte, France), Caroline Ferré and Alain Jalocha (Cilas, Orléans, France). The present work has benefited from the facilities and expertise of the Electron Micoscopy facilities of Imagerie-Gif (http://www.i2bc.paris-saclay.fr/spip.php?article282). This core facility is member of the Infrastructures en Biologie Santé et Agronomie (IBiSA), and is supported by the French national Research Agency under Investments for the Future programs “France-BioImaging”, and the Labex “Saclay Plant Science” (ANR-10-INSB-04-01 and ANR-11-IDEX-0003-02, respectively).

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Correspondence to Christine Vauthier.

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Varenne, F., Makky, A., Gaucher-Delmas, M. et al. Multimodal Dispersion of Nanoparticles: A Comprehensive Evaluation of Size Distribution with 9 Size Measurement Methods. Pharm Res 33, 1220–1234 (2016). https://doi.org/10.1007/s11095-016-1867-7

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KEY WORDS

  • light scattering
  • microscopy
  • nanoparticle tracking analysis
  • particle size distribution
  • tunable resistive pulse sensing