Abstract
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 language | English (US) |
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Article number | 2606 |
Journal | Nanomaterials |
Volume | 11 |
Issue number | 10 |
DOIs | |
State | Published - Oct 3 2021 |
Keywords
- Data-driven models
- Drug delivery
- Imaging flow cytometry
- Nanomedicine
- Nanoparticle dosimetry
- Pharmacokinetics
ASJC Scopus subject areas
- General Chemical Engineering
- General Materials Science