A mathematical framework for mechanically controlled brain drug delivery
File(s)
Author(s)
Yuan, Tian
Type
Thesis
Abstract
Neurological disorders have been a global health challenge, necessitating the imperative for the development of effective treatments. While pharmacotherapy is a common treatment for various brain diseases, delivering drugs into the brain is challenging; because the Blood-Brain Barrier (BBB), which prevents harmful substances in the blood from entering the brain, also blocks most of the conventional drug molecules. Despite the development of novel techniques, such as Convection-Enhanced Delivery (CED), to bypass the BBB by delivering drugs directly into the target area via catheters, achieving the desired drug distribution in the brain remains challenging. This is because the anisotropic and heterogeneous drug delivery pathways in the brain are formed by the extremely soft neurons, making the fluid and mass transport within the brain extremely complex, unsteady, and hard to predict. Therefore, highly efficient drug delivery in the brain relies on a fundamental understanding of how drugs interact with the micro-channels and how the microscale drug-neuron interactions affect the macroscale drug transport process in the brain.
To fill these gaps, this thesis has established a new multiscale and multiphysics mathematical framework underpinned by experiments carried out at different scales to provide accurate predictions for the drug delivery process in the brain. By achieving this goal, I have successfully: (i) gained a deeper understanding of the drug-brain interactions across the scales, and developed consistent mathematical formulations to describe them; (ii) built a technique to correlate the drug-neuron interactions to drug transport properties in the brain; (iii) established a multiscale framework to predict the drug delivery process in the brain; (iv) corroborated the models by experiments at different scales and validated the whole framework by in vivo drug delivery experiments with sheep; (v) investigated the effects of some important parameters of CED on the drug distribution in the brain.
To fill these gaps, this thesis has established a new multiscale and multiphysics mathematical framework underpinned by experiments carried out at different scales to provide accurate predictions for the drug delivery process in the brain. By achieving this goal, I have successfully: (i) gained a deeper understanding of the drug-brain interactions across the scales, and developed consistent mathematical formulations to describe them; (ii) built a technique to correlate the drug-neuron interactions to drug transport properties in the brain; (iii) established a multiscale framework to predict the drug delivery process in the brain; (iv) corroborated the models by experiments at different scales and validated the whole framework by in vivo drug delivery experiments with sheep; (v) investigated the effects of some important parameters of CED on the drug distribution in the brain.
Version
Open Access
Date Issued
2023-10-19
Date Awarded
2024-01-01
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Dini, Daniele
Sponsor
Imperial College London
China Scholarship Council
Publisher Department
Mechanical Engineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)