Computational Methodology for Drug Delivery to the Inner Ear Using Magnetic Nanoparticle Aggregates.

Background and objective: The main goal of the proposed study is to improve the efficiency of the ear treatment via targeted drug delivery to the inner ear, i.e. the cochlea. Although pharmacotherapy has been proposed as a solution to prevent damage or restore functionality to hair cells, the main challenge in such treatments is ensuring adequate drug delivery to the cells. To this end, we present a methodology for the evaluation of the magnetic forces needed to move magnetic particle nanorobots (abbreviated as MNP) and their aggregates through the cochlea round window membrane (RWM). Methods: The FEM - Lagrangian-Eulerian approach (Abaqus software) was used to determine the specific parameters of movement of the nanoparticles crossing the RWM. This method results in a high consistency of FEM simulations and in-vivo experimental results in regards to the required magnetic force during the movement of spherical nanoparticles with a given viscosity eta(ave). Based on the analysis of the experimental studies found in subject literature, the sizes of the MNPs and their aggregates able to cross RWM with and without the application of magnetic force F-M have been determined. Results: The present work accounts for both the experimental and theoretical aspects of these investigations. Presented research confirms the definite usability of the Lagrange-Euler method for the precise determination of the required magnetic force value FM to control the accelerated motion of MNP aggregates of complex shapes through RWM. It is possible to determine the predominant parameters with a precision of less than 5% for single-layer aggregates and spatial aggregates crossing the RWM. It can be concluded that the MNPs and their aggregates should not be larger than 500-750 nm to cross the RWM with high velocities of penetration close to 800 nm/s for magnetic forces of hundreds 10(-14) Newtons. Conclusions: The proposed Lagrangian-Eulerian approach is capable of accurately predicting the movement parameters of MNP aggregates of irregular shape that are close to the experimental test cases. The presented method can serve as a supplementary tool for the design of drug delivery systems to the inner ear using MNPs. (c) 2022 Published by Elsevier B.V.