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Methods and Study Designs for Characterizing the Pharmacokinetics and Pharmacodynamics of Carrier-Mediated Agents

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Targeted Drug Delivery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1831))

Abstract

Major advances in carrier-mediated agents (CMAs), which include nanoparticles, nanosomes, and conjugates, have revolutionized drug delivery capabilities over the past decade. While providing numerous advantages, such as greater solubility, duration of exposure, and delivery to the site of action over their small molecule counterparts, there is substantial variability in systemic clearance and distribution, tumor delivery, and pharmacologic effects (efficacy and toxicity) of these agents. In this chapter, we focus on the analytical and phenotypic methods required to design a study that characterizes the pharmacokinetics (PK) and pharmacodynamics (PD) of all forms of these nanoparticle-based drug agents. These methods include separation of encapsulated and released drugs, ultrafiltration for measurement of non-protein bound active drug, microdialysis to measure intra-tumor drug concentrations, immunomagnetic separation and flow cytometry for sorting cell types, and evaluation of spatial distribution of drug forms relative to tissue architecture by mass spectrometry imaging and immunohistochemistry.

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Acknowledgments

We thank Amanda Van Swearingen, Maria Sambade, and Carey Anders (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill (UNC)) for the TNBC spleen samples; the UNC Mouse Phase 1 Unit (UNC) for the T11 spleen samples; the Animal Studies Core (UNC) for animal handling; Andrew Madden, Gina Song, Allison Schorzman, and William Zamboni (UNC Eshelman School of Pharmacy) for study design and sample processing; and Guillaume Robichaud, Jeremy Barry, and David Muddiman (Department of Chemistry, North Carolina State University) for MALDESI MSI analysis.

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Authors and Affiliations

  1. Translational Oncology and Nanoparticle Drug Development Initiative (TOND2I) Lab, UNC Eshelman School of Pharmacy, UNC Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Allison N. Schorzman, Andrew T. Lucas, John R. Kagel & William C. Zamboni

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  1. Allison N. Schorzman
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  2. Andrew T. Lucas
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  4. William C. Zamboni
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Correspondence to William C. Zamboni .

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Editors and Affiliations

  1. Vivian L. Smith Department of Neurosurgery, University of Texas Health Science, Center at Houston, Houston, Texas, USA

    Rachael W. Sirianni

  2. Department of Mechanical Engineering, Virginia Tech, Blacksburg, Virginia, USA

    Bahareh Behkam

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Schorzman, A.N., Lucas, A.T., Kagel, J.R., Zamboni, W.C. (2018). Methods and Study Designs for Characterizing the Pharmacokinetics and Pharmacodynamics of Carrier-Mediated Agents. In: Sirianni, R., Behkam, B. (eds) Targeted Drug Delivery. Methods in Molecular Biology, vol 1831. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8661-3_15

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  • DOI: https://doi.org/10.1007/978-1-4939-8661-3_15

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  • Publisher Name: Humana Press, New York, NY

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  • Online ISBN: 978-1-4939-8661-3

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