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Sizing up the Next Generation of Nanomedicines

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Abstract

During the past two decades the nanomedicine field has experienced significant progress. To date, over sixty nanoparticle (NP) formulations have been approved in the US and EU while many others are in clinical or preclinical development, indicating a concerted effort to translate promising bench research to commercially viable pharmaceutical products. The use of NPs as novel drug delivery systems, for example, can improve drug safety and efficacy profiles and enable access to intracellular domains of diseased cells, thus paving the way to previously intractable biological targets. However, the measurement of their physicochemical properties presents substantial challenges relative to conventional injectable formulations. In this perspective, we focus exclusively on particle size, a core property and critical quality attribute of nanomedicines. We present an overview of relevant state-of-the-art technologies for particle sizing, highlighting the main parameters that can influence the selection of techniques suitable for a specific size range or material. We consider the increasing need, and associated challenge, to measure size in physiologically relevant media. We detail the importance of standards, key to validate any measurement, and the need for suitable reference materials for processes used to characterize novel and complex NPs. This perspective highlights issues critical to achieve compliance with regulatory guidelines and to support research and manufacturing quality control.

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Abbreviations

CDER:

FDA Center for Drug Evaluation and Research

EMA:

European Medicine Agency

FDA:

US Food and Drug Administration

ISO:

International Organization for Standardization

JRC:

European Commission Joint Research Centre

NIST:

National Institute of Standards and Technology

US NCL:

US National Cancer Institute, Nanotechnology Characterization Laboratory

EU NCL:

European Union NanoMedicine Characterization Laboratory

SRM:

Standard Reference Material (NIST trademarked product)

RM:

Reference Material

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ACKNOWLEDGMENTS AND DISCLOSURES

J.D.C., V.A.H., A.P-M, S.P. and P.L.S. would like to thank all of the speakers who participated in the ACS symposium on “Particle Sizing of Nanoparticles: From Regulatory & Metrology Aspects to Application & Analysis” in Boston, MA and the speakers who participated in the two symposia organized at CLINAM 2018 in Basel, Switzerland. The authors thank Joseph Meyer, Leidos Biomedical Research, Inc., for graphic illustrations. The authors confirm that this article has no conflict of interest to declare in the contents of the manuscript. The identification of any commercial product or trade name does not imply endorsement or recommendation by the National Institute of Standards and Technology, the Nanotechnology Characterization Lab, AstraZeneca or Pfizer.

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Authors and Affiliations

  1. Nanotechnology Characterization Laboratory (NCL), Leidos Biomedical Research, Inc., Frederick, Maryland, USA

    Jeffrey D. Clogston

  2. National Institute of Standards and Technology (NIST), Gaithersburg, Maryland, USA

    Vincent A. Hackley

  3. Trinity College Dublin, Dublin, Ireland

    Adriele Prina-Mello

  4. AstraZeneca UK LTD, Cambridge, UK

    Sanyogitta Puri & Silvia Sonzini

  5. Pfizer Inc., Novel Delivery Technologies- PhRD, 68 Lowell Junction Road, Andover, Massachusetts, USA

    Patrick Lim Soo

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  1. Jeffrey D. Clogston
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  2. Vincent A. Hackley
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  3. Adriele Prina-Mello
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  4. Sanyogitta Puri
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  5. Silvia Sonzini
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  6. Patrick Lim Soo
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Correspondence to Jeffrey D. Clogston or Patrick Lim Soo.

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Clogston, J.D., Hackley, V.A., Prina-Mello, A. et al. Sizing up the Next Generation of Nanomedicines. Pharm Res 37, 6 (2020). https://doi.org/10.1007/s11095-019-2736-y

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