TY - JOUR
T1 - A mathematical model to predict nanomedicine pharmacokinetics and tumor delivery
AU - Dogra, Prashant
AU - Butner, Joseph D.
AU - Ruiz Ramírez, Javier
AU - Chuang, Yao li
AU - Noureddine, Achraf
AU - Jeffrey Brinker, C.
AU - Cristini, Vittorio
AU - Wang, Zhihui
N1 - Funding Information:
This research has been supported in part by the National Science Foundation Grant DMS-1930583 (VC, ZW), the National Institutes of Health (NIH) Grants 1U01CA196403 (VC, ZW), 1U01CA213759 (VC, ZW), 1R01CA226537 (CJB, VC, ZW), 1R01CA222007 (VC, ZW), and U54CA210181 (VC, ZW). P.D. acknowledges S. Nizzero, M.J. Peláez, and S. Goel for helpful scientific discussions.
Publisher Copyright:
© 2020 The Authors
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - Towards clinical translation of cancer nanomedicine, it is important to systematically investigate the various parameters related to nanoparticle (NP) physicochemical properties, tumor characteristics, and inter-individual variability that affect the tumor delivery efficiency of therapeutic nanomaterials. Comprehensive investigation of these parameters using traditional experimental approaches is impractical due to the vast parameter space; mathematical models provide a more tractable approach to navigate through such a multidimensional space. To this end, we have developed a predictive mathematical model of whole-body NP pharmacokinetics and their tumor delivery in vivo, and have conducted local and global sensitivity analyses to identify the factors that result in low tumor delivery efficiency and high off-target accumulation of NPs. Our analyses reveal that NP degradation rate, tumor blood viscosity, NP size, tumor vascular fraction, and tumor vascular porosity are the key parameters in governing NP kinetics in the tumor interstitium. The impact of these parameters on tumor delivery efficiency of NPs is discussed, and optimal values for maximizing NP delivery are presented.
AB - Towards clinical translation of cancer nanomedicine, it is important to systematically investigate the various parameters related to nanoparticle (NP) physicochemical properties, tumor characteristics, and inter-individual variability that affect the tumor delivery efficiency of therapeutic nanomaterials. Comprehensive investigation of these parameters using traditional experimental approaches is impractical due to the vast parameter space; mathematical models provide a more tractable approach to navigate through such a multidimensional space. To this end, we have developed a predictive mathematical model of whole-body NP pharmacokinetics and their tumor delivery in vivo, and have conducted local and global sensitivity analyses to identify the factors that result in low tumor delivery efficiency and high off-target accumulation of NPs. Our analyses reveal that NP degradation rate, tumor blood viscosity, NP size, tumor vascular fraction, and tumor vascular porosity are the key parameters in governing NP kinetics in the tumor interstitium. The impact of these parameters on tumor delivery efficiency of NPs is discussed, and optimal values for maximizing NP delivery are presented.
KW - Cancer nanotherapy
KW - Enhanced permeability and retention effect
KW - Mechanistic mathematical modeling
KW - PBPK
KW - Pharmacokinetics
KW - Sensitivity analysis
UR - http://www.scopus.com/inward/record.url?scp=85081650033&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85081650033&partnerID=8YFLogxK
U2 - 10.1016/j.csbj.2020.02.014
DO - 10.1016/j.csbj.2020.02.014
M3 - Article
AN - SCOPUS:85081650033
SN - 2001-0370
VL - 18
SP - 518
EP - 531
JO - Computational and Structural Biotechnology Journal
JF - Computational and Structural Biotechnology Journal
ER -