Abstract
Nanoparticles provide a promising approach for the targeted delivery of therapeutic, diagnostic and imaging agents in the body. However, it is not yet fully understood how the physico-chemical properties of the nanoparticles influence cellular association and uptake. Cellular association experiments are routinely performed in an effort to determine how nanoparticle properties impact the rate of nanoparticle–cell association. To compare experiments in a meaningful manner, the association data must be normalized by the amount of nanoparticles that arrive at the cells, a measure referred to as the delivered dose. The delivered dose is calculated from a model of nanoparticle transport through fluid. A standard assumption is that all nanoparticles within the population are monodisperse, namely the nanoparticles have the same physico-chemical properties. We present a semi-analytic solution to a modified model of nanoparticle transport that allows for the nanoparticle population to be polydisperse. This solution allows us to efficiently analyse the influence of polydispersity on the delivered dose. Combining characterization data obtained from a range of commonly used nanoparticles and our model, we find that the delivered dose changes by more than a factor of 2 if realistic amounts of polydispersity are considered.
Highlights
Nanoparticles are a promising tool in the field of biomedicine, providing novel approaches for delivering agents in a targeted manner for therapeutic, imaging and diagnostic purposes [1 –7]
This is appropriate for a non-aggregating nanoparticle population in a fluid that does not contain proteins or if the nanoparticles are non-fouling, that is, proteins do not adsorb to the nanoparticles
The protein corona introduces the difference in hydrodynamic diameter, and we assume that all nanoparticles are synthesized with the same diameter
Summary
Nanoparticles are a promising tool in the field of biomedicine, providing novel approaches for delivering agents in a targeted manner for therapeutic, imaging and diagnostic purposes [1 –7]. Mahnama et al [30] present an analytic solution for the original sedimentation and diffusion model, and examine the 2 influence of the relative rates of sedimentation and diffusion on the delivered dose While insightful, this approach is limited to monodisperse populations and a single boundary condition. We calculate the delivered dose as a function of time and the size distribution parameters, typically given by the mean, m, and the standard deviation, s We note that this approach is different from the approach considered by Rodriguez-Lorenzo et al [37] to examine the influence of polydispersity. The model of Rodriguez-Lorenzo et al [37] can describe size-dependent adherence at the boundary; it is unclear how this would be implemented as a specific uptake rate
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