Data-driven modeling of the cellular pharmacokinetics of degradable chitosan-based nanoparticles

Huw D. Summers, Carla P. Gomes, Aida Varela-Moreira, Ana P. Spencer, Maria Gomez-Lazaro, Ana P. Pêgo, Paul Rees

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Nanoparticle drug delivery vehicles introduce multiple pharmacokinetic processes, with the delivery, accumulation, and stability of the therapeutic molecule influenced by nanoscale pro-cesses. Therefore, considering the complexity of the multiple interactions, the use of data-driven models has critical importance in understanding the interplay between controlling processes. We demonstrate data simulation techniques to reproduce the time-dependent dose of trimethyl chi-tosan nanoparticles in an ND7/23 neuronal cell line, used as an in vitro model of native peripheral sensory neurons. Derived analytical expressions of the mean dose per cell accurately capture the pharmacokinetics by including a declining delivery rate and an intracellular particle degradation process. Comparison with experiment indicates a supply time constant, τ = 2 h. and a degradation rate constant, b = 0.71 h−1. Modeling the dose heterogeneity uses simulated data distributions, with time dependence incorporated by transforming data-bin values. The simulations mimic the dynamic nature of cell-to-cell dose variation and explain the observed trend of increasing numbers of high-dose cells at early time points, followed by a shift in distribution peak to lower dose between 4 to 8 h and a static dose profile beyond 8 h.

Original languageEnglish (US)
Article number2606
Issue number10
StatePublished - Oct 3 2021


  • Data-driven models
  • Drug delivery
  • Imaging flow cytometry
  • Nanomedicine
  • Nanoparticle dosimetry
  • Pharmacokinetics

ASJC Scopus subject areas

  • Chemical Engineering(all)
  • Materials Science(all)


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