Multiphysics simulation of drug-coated balloon deployment and drug delivery

Fensterseifer Schmidt, André (2024) Multiphysics simulation of drug-coated balloon deployment and drug delivery. PhD thesis, University of Glasgow.

Abstract

The treatment of ischaemic arterial disease has improved substantially in recent decades largely due to the inclusion of local delivery of anti-restenotic drugs in percutaneous intervention. To perform drug delivery without an implant, a drug-coated balloon (DCB) is inflated endovascularly for a one-time drug transfer from its coating to the target artery upon contact, serving as an alternative or complementary therapy to drug-eluting stents. While this therapy may avoid the potential complications of implants, namely in-stent restenosis and thrombosis, its greatest challenge is providing sufficient drug delivery and subsequent retention in the tissue without sustained release from a permanent drug reservoir. The mechanisms of drug delivery from DCBs are not completely understood, and the literature lacks models that describe the mechanics and drug release parts of the problem simultaneously. Aiming to improve this understanding, this work proposes modelling efforts towards an in silico simulation framework of simultaneous DCB deployment and drug delivery that studies procedural parameters such as inflation pressure, inflation duration, and drug loading and their effect on drug delivery performance.

First, the foundation for the modelling assumptions is set with a drug delivery problem considering an idealised 2D-axisymmetric multilayered arterial wall and a prescribed set of boundary conditions to represent the DCB’s role. Then, a more realistic geometrical representation of a DCB is proposed based on the specifications of a DCB that has undergone clinical trials, along with the modelling of the inflation procedure and drug release from the coating. Ultimately, the two previous models are combined, culminating in a novel multiphysics simulation of DCB deployment that includes time-dependent structural mechanics, contact interaction, transmural filtration, and drug transport and retention simultaneously. All models are implemented in COMSOL Multiphysics® based on the finite element method. Results are assessed throughout the simulation of DCB deployment and 28-day follow-up, evaluating safety and efficacy indicators common to preclinical testing (drug content and receptor saturation) from the spatiotemporal drug distribution.

Although further studies and experimental data are still required to improve the model validation and achieve clinical utility, this work demonstrates the potential of in silico modelling as a powerful tool to complement traditional methods of medical device testing. The valuable mechanistic insights obtained can enhance the design process of DCBs and improve drug-delivery therapies, substantially reduce development costs, and expedite the technology.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Supported by funding from Biosensors International.
• Subjects: R Medicine > R Medicine (General); T Technology > TA Engineering (General). Civil engineering (General)
• Colleges/Schools: College of Science and Engineering > School of Engineering
• Supervisor's Name: Mcginty, Dr. Sean, Aggarwal, Dr. Ankush and Oldroyd, Dr. Keith
• Date of Award: 2024
• Depositing User: Theses Team
• Unique ID: glathesis:2024-84410
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 27 Jun 2024 09:58
• Last Modified: 27 Jun 2024 09:58
• Thesis DOI: 10.5525/gla.thesis.84410
• URI: https://theses.gla.ac.uk/id/eprint/84410