A mathematical model to predict nanomedicine pharmacokinetics and tumor delivery

Prashant Dogra, Joseph D. Butner, Javier Ruiz Ramírez, Yao li Chuang, Achraf Noureddine, C. Jeffrey Brinker, Vittorio Cristini, Zhihui Wang

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)518-531
Number of pages14
JournalComputational and Structural Biotechnology Journal
Volume18
DOIs
StatePublished - 2020

Keywords

  • Cancer nanotherapy
  • Enhanced permeability and retention effect
  • Mechanistic mathematical modeling
  • PBPK
  • Pharmacokinetics
  • Sensitivity analysis

ASJC Scopus subject areas

  • Biotechnology
  • Biophysics
  • Structural Biology
  • Biochemistry
  • Genetics
  • Computer Science Applications

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