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Quantitative Analysis of Cellular Drug Transport, Disposition, and Delivery

  • Book
  • © 2021

Overview

Editors:
  1. Gus R. Rosania

    1. College of Pharmacy, University of Michigan, Ann Arbor, USA

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    You can also search for this editor in PubMed   Google Scholar

  2. Greg M. Thurber

    1. Department of Chemical Engineering, University of Michigan, Ann Arbor, USA

    View editor publications

    You can also search for this editor in PubMed   Google Scholar

  • Includes cutting-edge techniques
  • Provides step-by-step detail essential for reproducible results
  • Features information that applies to a wide array of research areas

Part of the book series: Methods in Pharmacology and Toxicology (MIPT)

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Table of contents (18 protocols)

  1. Front Matter

    Pages i-xvii
    Download chapter PDF

  2. Small Molecules

    1. Front Matter

      Pages 1-1
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    2. Measurement of Transcellular Transport Rates and Intracellular Drug Sequestration in the Presence of an Extracellular Concentration Gradient

      • Kyoung Ah Min, Gus R. Rosania
      Pages 3-39

    3. Kinetic Design for Establishing Long-Term Stationary Cytosol Concentrations During Drug Transport across P-gp Expressing Confluent Cell Monolayers to Facilitate Measuring Cytosol Concentration, Fitting Drug Molar Partition Coefficients into the Cytosolic Monolayer of the Plasma Membrane, and Kinetically Identifying Drug Uptake Transporters

      • Joe Bentz
      Pages 41-65

    4. In Vitro Methodologies to Assess Potential for Transporter-Mediated Drug–Drug Interactions

      • Jibin Li, Qing Wang, Ismael J. Hidalgo
      Pages 67-80

    5. Determination of Fraction Unbound and Unbound Partition Coefficient to Estimate Intracellular Free Drug Concentration

      • Sangwoo Ryu, Keith Riccardi, Samantha Jordan, Nathaniel Johnson, Li Di
      Pages 81-96

    6. Quantitative Analysis of Intracellular Drug Concentrations in Hepatocytes

      • Chitra Saran, James J. Beaudoin, Nathan D. Pfeifer, Kim L. R. Brouwer
      Pages 97-125

    7. Quantification of Intracellular Drug Aggregates and Precipitates

      • Phillip Rzeczycki, Gus R. Rosania
      Pages 127-145

    8. Quantitative Phenotypic Analysis of Drug Sequestering Macrophage Subpopulations

      • Mikhail D. Murashov
      Pages 147-162

    9. Using an Integrated QSAR Model to Check Whether Small-Molecule Xenobiotics Will Accumulate in Biomembranes, with Particular Reference to Fluorescent Imaging Probes

      • Richard W. Horobin, Juan C. Stockert
      Pages 163-177

    10. Diversity-Oriented Fluorescence Library Approach (DOFLA) for Discovery of Cell-Permeable Probes for Applications in Live Cell Imaging

      • Dongdong Su, Young-Tae Chang
      Pages 179-197

  3. Macromolecules, Biologics, and Nanoparticles

    1. Front Matter

      Pages 199-199
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    2. Overcoming Cellular and Systemic Barriers to Design the Next Wave of Peptide Therapeutics

      • Jerome Hochman, Tomi Sawyer, Ruchia Duggal
      Pages 201-227

    3. Intracellular Targeting of Cyclotides for Therapeutic Applications

      • Nicole Lawrence, David J. Craik
      Pages 229-248

    4. Cellular Trafficking of Monoclonal and Bispecific Antibodies

      • John J. Rhoden, Christopher M. Wiethoff
      Pages 249-274

    5. Quantitative Drug Target Imaging Using Paired-Agent Principles

      • Kenneth M. Tichauer, Negar Sadeghipour, Yu “ Winston” Wang, Summer L. Gibbs, Jonathan T. C. Liu, Kimberley S. Samkoe
      Pages 275-304

    6. Quantitative Determination of Intracellular Bond Cleavage

      • Joshua A. Walker, Michelle R. Sorkin, Christopher A. Alabi
      Pages 305-330

    7. Development and Application of a Single Cell-Level PK-PD Model for ADCs

      • Shufang Liu, Dhaval K. Shah
      Pages 331-355

    8. Contribution of Nontarget Cells to the Disposition, Antitumor Activity, and Antigen-Independent Toxicity of Antibody–Drug Conjugates

      • David W. Meyer, Fu Li, Robert P. Lyon
      Pages 357-382

    9. Tracking siRNA–Nanocarrier Assembly and Disassembly Using FRET

      • Lorenz Isert, Aditi Mehta, Friederike Adams, Olivia M. Merkel
      Pages 383-396
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Keywords

About this book

This thorough book explores some of the most important methods and concepts affecting the quantitative analysis of the transport, targeting, and disposition of chemicals within cells, which in turn impact the macroscopic pharmacokinetics of chemical agents in the whole organism. The first half of the volume focuses on small organic molecules with drug-like characteristics, while the second half delves into the cellular pharmacokinetics of biologics and other macromolecules, including peptide therapeutics, cyclotides, antibodies, as well as nanoparticles, thus creating a comprehensive treatise that approaches cellular pharmacokinetics from the different perspectives of pharmaceutical scientists, chemical biologists, medicinal chemists, and protein engineers dealing with very different chemical agents spanning a wide range of sizes, physicochemical properties, and targeting mechanisms. Written for the Methods in Pharmacology and Toxicology series, chapters provide the kind of key detail and expert implementation advice that leads to excellent results in the lab. Synthetic biologists, biophysicists, and bioengineers are amongst the long list of scientists who could benefit from reading this book or from using it as a textbook. 

Authoritative and practical, Quantitative Analysis of Cellular Drug Transport, Disposition, and Delivery builds on a long history of drug development and the adding of quantitative methods at the cellular scale in order to inspire new approaches to drug development that are better able to take advantage of phenomena such as soluble-to-insoluble phase transitions or bispecific targeting, which could ultimately be exploited for the development of more effective drug delivery systems and therapeutic agents.

Editors and Affiliations

  • College of Pharmacy, University of Michigan, Ann Arbor, USA

    Gus R. Rosania

  • Department of Chemical Engineering, University of Michigan, Ann Arbor, USA

    Greg M. Thurber

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