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

Date
2016
Authors
Dogruoz, E.
Dayanik, S.
Budak, G.
Sabuncuoglu, I.
Advisor
Supervisor
Co-Advisor
Co-Supervisor
Instructor
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
Journal Title
Journal ISSN
Volume Title
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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.

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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
Citation
Published Version (Please cite this version)