Understanding nanoparticle flow with a new in vitro experimental and computational approach using hydrogel channels

Abstract

Nanoparticles (NPs) are considered as one of the most promising drug delivery vehicles and a next-generation solution for current medical challenges. In this context, variables related to flow of NPs such as the quantity of NPs lost during transport and flow trajectory greatly affect the clinical efficiency of NP drug delivery systems. Currently, there is little knowledge of the physical mechanisms dominating NP flow inside the human body due to the limitations of available experimental tools for mimicking complex physiological environments at the preclinical stage. Here, we report a coupled experimental and computational fluid dynamics (CFD)-based novel in vitro approach to predict the flow velocity and binding of NP drug delivery systems during transport through vasculature. Poly(hydroxyethyl)methacrylate hydrogels were used to form soft cylindrical constructs mimicking vascular sections as flow channels for synthesized iron oxide NPs in these first-of-its-kind transport experiments. Brownian dynamics and material of the flow channels played key roles in NP flow, based on the measurements of NP flow velocity over seven different mass concentrations. A fully developed laminar flow of the NPs under these conditions was simultaneously predicted using CFD. Results from the mass loss of NPs during flow indicated a diffusion-dominated flow at higher particle concentrations but a flow controlled by the surrounding fluid and Brownian dynamics at the lowest NP concentrations. The CFD model predicted a mass loss of 1.341% and 6.253% for the 4.12 g·mL−1 and 2.008 g·mL−1 inlet mass concentrations of the NPs, in close confirmation with the experimental results. This further highlights the reliability of our new in vitro technique in providing mechanistic insights of NP flow for potential preclinical stage applications.

A Novel Experimental Approach to Understand the Transport of Nanodrugs

“…The mass loss, however, shows a slight decrease in this size range, which implies that competing diffusion and sedimentation mechanisms control the nanodrug transport in this size regime. The decrease in deposition for the 302 nm sized nanodrugs can be explained in terms of an increase in diffusivity of the combined nanodrug as compared to the zinc oxide nanodrug, as seen from the trend in the velocity profile [33,39,40,49].…”

“…Three different nanodrug compositions including iron oxide, zinc oxide, and Cu-Zn-Fe oxide coated with biocompatible ligands were synthesized via a modified polyol method using a Schlenk line technique, similar to our previously reported protocol [39,40]. These three new metal oxide compositions served as model nanodrugs of varying sizes for subsequent experiments to investigate the transport of nanodrugs (Supplementary Materials, Figure S1).…”

“…The group used the translational and rotational diameter to determine this overall effect of nanoparticle shape on transport properties and a rigid multi-blob method to discretize the nanoparticle systems for solution. We have previously reported a combined computational and experimental approach to predict the velocity and deposition of nanodrugs through various types of flow channels including straight, circular, and hydrogel-based [39,40]. However, these flow channels did not account for the blood vessels or biomolecules that lie in the path of the nanodrugs in real vascular or pulmonary arterial environment [41].…”

A Dynamic Light Scattering Approach for Detection of Nanomaterials in Tennessee River

“…However, we established key analysis criteria of the DLS results for suitably investigating nanomaterials in environmental samples using two different synthesized iron oxide nanoparticle solutions as references. The iron oxide nanoparticles were synthesized with different ratios of polyvinyl pyrrolidone (PVP) and polyethyleneimine (PEI) polymer coatings following a previously reported protocol (supporting information) (Boutchuen et al., 2020; Palchoudhury et al., 2018). These two nanomaterials were first analyzed in the DLS at environmentally relevant concentrations (0.1 μg L −1 ).…”