Image‐guided mathematical modeling for pharmacological evaluation of nanomaterials and monoclonal antibodies

Abstract

While plasma concentration kinetics has traditionally been the predictor of drug pharmacological effects, it can occasionally fail to represent kinetics at the site of action, particularly for solid tumors. This is especially true in the case of delivery of therapeutic macromolecules (drug‐loaded nanomaterials or monoclonal antibodies), which can experience challenges to effective delivery due to particle size‐dependent diffusion barriers at the target site. As a result, disparity between therapeutic plasma kinetics and kinetics at the site of action may exist, highlighting the importance of target site concentration kinetics in determining the pharmacodynamic effects of macromolecular therapeutic agents. Assessment of concentration kinetics at the target site has been facilitated by non‐invasive in vivo imaging modalities. This allows for visualization and quantification of the whole‐body disposition behavior of therapeutics that is essential for a comprehensive understanding of their pharmacokinetics and pharmacodynamics. Quantitative non‐invasive imaging can also help guide the development and parameterization of mathematical models for descriptive and predictive purposes. Here, we present a review of the application of state‐of‐the‐art imaging modalities for quantitative pharmacological evaluation of therapeutic nanoparticles and monoclonal antibodies, with a focus on their integration with mathematical models, and identify challenges and opportunities. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Diagnostic Tools > in vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

Innate immunity plays a key role in controlling viral load in COVID-19: mechanistic insights from a whole-body infection dynamics model

“…Based on the estimated characteristic times (1-24 h) of the vascular transport processes (shown in Figure 1 and presented as rates in Table 2), it can be inferred that viral transport is permeability-limited and not perfusionlimited, i.e., capillary permeability and vascular surface area govern the rate of extravasation of virions from blood vessels into tissue interstitium to reach the target cells, and thus viral transport is not exclusively governed by the plasma flow rates into the organs. This is consistent with the in vivo behavior of nanomaterials of comparable size [35][36][37][38][39][40] , and is in contrast to the perfusion ratelimited kinetics of smaller lipophilic molecules. The variability in characteristic times of vascular transport can be explained by differences in the permeability of capillary endothelium due to differences in pore sizes of endothelial fenestrae 41 .…”

A continuum mechanical framework for modeling tumor growth and treatment in two- and three-phase systems

“…Models with some similarities to those detailed herein are being used for successful medical applications (e.g. [6,38]), and extensions to clinical applications of drug delivery and evaluation of drug efficiency are also possible; initial works in these directions can be found in [4,10].…”

Highway to Success—Developing Advanced Polymer Therapeutics

“…The use of image‐guided mathematical modeling for pharmacological evaluation of nanomaterials has been recently reviewed by Dogra et al. [ 148 ] An integrated SPECT/CT imaging‐based pharmacokinetics mathematical model to evaluate the disposition of mesoporous silica nanoparticles has been developed. [ 149 ]…”

“…[56] Non-invasive in vivo imaging permits both the visualization and quantification of the in vivo disposition of nanoparticles and is crucial for a comprehensive understanding of their distribution. The use of image-guided mathematical modeling for pharmacological evaluation of nanomaterials has been recently reviewed by Dogra et al [148] An integrated SPECT/CT imaging-based pharmacokinetics mathematical model to evaluate the disposition of mesoporous silica nanoparticles has been developed. [149] Mass spectrometry imaging (MSI) is a powerful label-free tool that can map the nanocarrier, the drug, and its pharmacodynamic effect in tissues therefore providing critical additional data to deepen mechanistic understanding.…”