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      Analysis of the in vitro nanoparticle–cell interactions via a smoothing-splines mixed-effects model

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      Author
      Dogruoz, E.
      Dayanik, S.
      Budak, G.
      Sabuncuoglu, I.
      Date
      2016
      Source Title
      Artificial Cells, Nanomedicine and Biotechnology
      Print ISSN
      2169-1401
      Electronic ISSN
      2169-141X
      Publisher
      Taylor and Francis
      Volume
      44
      Issue
      3
      Pages
      800 - 810
      Language
      English
      Type
      Article
      Item Usage Stats
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      102
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      Abstract
      A mixed-effects statistical model has been developed to understand the nanoparticle (NP)–cell interactions and predict the rate of cellular uptake of NPs. NP–cell interactions are crucial for targeted drug delivery systems, cell-level diagnosis, and cancer treatment. The cellular uptake of NPs depends on the size, charge, chemical structure, and concentration of NPs, and the incubation time. The vast number of combinations of these variable values disallows a comprehensive experimental study of NP–cell interactions. A mathematical model can, however, generalize the findings from a limited number of carefully designed experiments and can be used for the simulation of NP uptake rates, to design, plan, and compare alternative treatment options. We propose a mathematical model based on the data obtained from in vitro interactions of NP–healthy cells, through experiments conducted at the Nanomedicine and Advanced Technologies Research Center in Turkey. The proposed model predicts the cellular uptake rate of silica, polymethyl methacrylate, and polylactic acid NPs, given the incubation time, size, charge and concentration of NPs. This study implements the mixed-model methodology in the field of nanomedicine for the first time, and is the first mathematical model that predicts the rate of cellular uptake of NPs based on sound statistical principles. Our model provides a cost-effective tool for researchers developing targeted drug delivery systems.
      Keywords
      Linear mixed model
      Nanomedicine
      Nanoparticle uptake rate
      Smoothing splines
      Targeted drug delivery
      Cells
      Contour measurement
      Cost effectiveness
      Medical nanotechnology
      Nanoparticles
      Polymethyl methacrylates
      Telemetering
      Designed experiments
      Linear mixed models
      Nanoparticle uptakes
      Smoothing spline
      Statistical modeling
      Statistical principles
      Targeted drug delivery systems
      Permalink
      http://hdl.handle.net/11693/36564
      Published Version (Please cite this version)
      http://dx.doi.org/10.3109/21691401.2015.1011811
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