Quantitative Analysis of Cellular Drug Transport, Disposition, and Delivery

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.

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

Inhalt
Measurement of Transcellular Transport Rates and Intracellular Drug Sequestration in the Presence of an Extracellular Concentration Gradient.- 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.- In Vitro Methodologies to Assess Potential for Transporter-Mediated Drug-Drug Interactions.- Determination of Fraction Unbound and Unbound Partition Coefficient to Estimate Intracellular Free Drug Concentration.- Quantitative Analysis of Intracellular Drug Concentrations in Hepatocytes.- Quantification of Intracellular Drug Aggregates and Precipitates.- Quantitative Phenotypic Analysis of Drug Sequestering Macrophage Subpopulations.- Using an Integrated QSAR Model to Check Whether Small-Molecule Xenobiotics Will Accumulate in Biomembranes, with Particular Reference to Fluorescent Imaging Probes.- Diversity-Oriented Fluorescence Library Approach (DOFLA) for Discovery of Cell-Permeable Probes for Applications in Live Cell Imaging.- Overcoming Cellular and Systemic Barriers to Design the Next Wave of Peptide Therapeutics.- Intracellular Targeting of Cyclotides for Therapeutic Applications.- Cellular Trafficking of Monoclonal and Bispecific Antibodies.- Quantitative Drug Target Imaging Using Paired-Agent Principles.- Quantitative Determination of Intracellular Bond Cleavage.- Development and Application of a Single Cell-Level PK-PD Model for ADCs.- Contribution of Non-Target Cells to the Disposition, Antitumor Activity, and Antigen-Independent Toxicity of Antibody Drug-Conjugates.- Tracking siRNA-Nanocarrier Assembly and Disassembly Using FRET.- Sub-Cellular Drug Depots as Reservoirs for Small Molecule Drugs. <p