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Understanding Nanomedicine Size and Biological Response Dependency: What Is the Relevance of Previous Relationships Established on Only Batch-Mode DLS-Measured Sizes?

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Abstract

Purpose

Most relationships between size and nanomedicine performance and safety were established before the early 2010s’ when batch-mode dynamic light scattering (batch-mode DLS) was the only easy size measurement method for colloids available. They are basis for the rational design of nanomedicines, but misunderstood contrasting results are reported. This work aimed to investigate whether these relationships can be used with confidence knowing that batch-mode DLS can be tricky when measuring sizes of polydisperse systems.

Methods

A polydisperse dispersion of polymer nanoparticles ranging from 100 to 465 nm was synthesized. The particles were separated in 4 fractions by successive centrifugations. The capacity of each fraction and parent dispersion to activate the complement system was evaluated by Crossed immuno-electrophoresis.

Results

Each fraction was a population of particles with a distinct size. It showed a different capacity to activate the complement system. Particles of the fractions showing the strongest capacity to activate the complement systems had a different size evaluated by batch-mode DLS then that of the parent particles.

Conclusion

Particles activating the complement system in the parent dispersion were not those that were detected by batch-mode DLS while measuring its size. This work pointed out that previously established relationships between nanomedicine size and their biological response should be taken with caution if sizes were only measured by batch-mode DLS.

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Abbreviations

DLS:

Dynamic light scattering

C3A50:

Concentration in particles expressed in cm2.mL−1 required to activate 50% of the protein C3 of the complement system in the experimental conditions of the test.

EDTA:

Ethylene diamine tetraacetic acid

EGTA:

Ethylene glycol tetraacetic acid

IBCA:

Isobutylcyanoacrylate

ISO:

International Standard Organization

PdI:

Polydispersity Index

PIBCA:

Poly(isobutylcyanoacrylate)

SDV:

Standard deviation

SOP:

Standard operating conditions

TEM:

Transmission electron microscopy

TRPS:

Tunable resistive pulse sensing

VBS2+ :

Veronal buffer supplemented with calcium (0.15 mM) and magnesium (0.5 mM)

VBS5X:

Veronal buffer concentrated by 5 times.

VBS-EDTA:

Veronal buffer supplemented with EDTA (40 mM)

VBS-EGTA+Mg2+ :

Veronal buffer supplemented with EGTA (10 mM) and magnesium (2.5 mM)

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  1. Institut Galien Paris Saclay, Université Paris-Saclay, CNRS, 92296, Chatenay-Malabry, France

    Elquio Eleamen Oliveira, Maryème Barendji & Christine Vauthier

  2. Centro de Ciências Biológicas e Sociais Aplicadas, Universidade Estadual da Paraíba, João Pessoa, Paraíba, Brazil

    Elquio Eleamen Oliveira

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Eleamen Oliveira, E., Barendji, M. & Vauthier, C. Understanding Nanomedicine Size and Biological Response Dependency: What Is the Relevance of Previous Relationships Established on Only Batch-Mode DLS-Measured Sizes?. Pharm Res 37, 161 (2020). https://doi.org/10.1007/s11095-020-02869-x

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