Publicação

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

Detalhes bibliográficos
Resumo: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, t = 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.
Assunto:Drug delivery Imaging flow cytometry Nanoparticle dosimetry Data-driven models Pharmacokinetics Nanomedicine
País:Portugal
Tipo de documento:journal article
Tipo de acesso:Aberto
Instituição associada:Repositório Aberto da Universidade do Porto
Idioma:inglês
Origem:Repositório Aberto da Universidade do Porto

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