West, Hannah Jordan;
(2022)
A computational investigation of nanoparticle-mediated drug
delivery in preclinical scenarios.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Polymersomes have been identified as a promising vesicle for nanoparticle-mediated chemotherapy delivery, which has been shown to increase treatment efficacy and reduce off target side effects, compared to freely administering the agent, when treating solid tumours. In this thesis mathematical models are developed and used to simulate chemotherapy drug delivery via polymersomes, in a range of preclinical environments. The preclinical environments are chosen to mimic the therapeutic development process and to identify key properties of polymersomes, that can be fed into experimental design and testing, in order to focus developments. In the simplest scenario, representative of cell monolayers, analytical solutions are derived to determine the optimal physical properties of the polymersomes. In the most complex scenario, representative of in vivo environments where spatial heterogeneity must be accounted for, whole system properties are investigated, such as blood concentrations and diffusivity through tissue. Chemotherapy delivery, without polymersomes, is also considered to enable comparison between delivery mechanisms. In these in vivo scenarios graphical networks are used to represent blood vessels. These graphical networks are derived from real blood vessels via biomedical imaging and analysis processes. In addition to mathematical model development, we consider the influence of this image analysis process on the properties of the graphical blood vessel networks. In particular we focus on the how the choice of segmentation and skeletonisation technique influences the properties of the graphical blood vessel networks.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | A computational investigation of nanoparticle-mediated drug delivery in preclinical scenarios |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng UCL > Provost and Vice Provost Offices > UCL BEAMS UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10150043 |
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