Analysis of the in vitro nanoparticle–cell interactions via a smoothing-splines mixed-effects model
Date
2016Source 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
ArticleItem Usage Stats
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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 modelNanomedicine
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