Quantitative Analysis of Cellular Drug Transport, Disposition, and Delivery

ISBN-13: 9781071612521 / Angielski / Miękka / 2021

Opis

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.

Spis treści

Part I: Small Molecules

 

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

            Kyoung Ah Min and Gus R. Rosania

 

2. 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

 

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

            Jibin Li, Qing Wang, and Ismael J. Hidalgo

 

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

            Sangwoo Ryu, Keith Riccardi, Samantha Jordan, Nathaniel Johnson, and Li Di

 

5. Quantitative Analysis of Intracellular Drug Concentrations in Hepatocytes

            Chitra Saran, James J. Beaudoin, Nathan D. Pfeifer, and Kim L.R. Brouwer

 

6. Quantification of Intracellular Drug Aggregates and Precipitates

            Phillip Rzeczycki and Gus R. Rosania

 

7. Quantitative Phenotypic Analysis of Drug Sequestering Macrophage Subpopulations

            Mikhail D. Murashov

 

8. 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 and Juan C. Stockert

 

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

            Dongdong Su and Young-Tae Chang

 

Part II: Macromolecules, Biologics, and Nanoparticles

 

10. Overcoming Cellular and Systemic Barriers to Design the Next Wave of Peptide Therapeutics

            Jerome Hochman, Tomi Sawyer, and Ruchia Duggal

 

11. Intracellular Targeting of Cyclotides for Therapeutic Applications

            Nicole Lawrence and David J. Craik

 

12. Cellular Trafficking of Monoclonal and Bispecific Antibodies

            John J. Rhoden and Christopher M. Wiethoff

 

13. Quantitative Drug Target Imaging Using Paired-Agent Principles

            Kenneth M. Tichauer, Negar Sadeghipour, Yu “Winston” Wang, Summer L. Gibbs, Jonathan T.C. Liu, and Kimberley S. Samkoe

 

14. Quantitative Determination of Intracellular Bond Cleavage

            Joshua A. Walker, Michelle R. Sorkin, and Christopher A. Alabi

 

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

            Shufang Liu and Dhaval K. Shah

 

16. Contribution of Non-Target Cells to the Disposition, Antitumor Activity, and Antigen-Independent Toxicity of Antibody Drug-Conjugates

            David W. Meyer, Fu Li, and Robert P. Lyon

 

17. Tracking siRNA-Nanocarrier Assembly and Disassembly Using FRET

            Lorenz Isert, Aditi Mehta, Friederike Adams, and Olivia M. Merkel

 

18. Sub-Cellular Drug Depots as Reservoirs for Small Molecule Drugs

            Ran Li, Ralph Weissleder, and Miles A. Miller