| dc.date.accessioned | 2022-11-28T15:01:35Z | |
| dc.date.available | 2022-11-28T15:01:35Z | |
| dc.date.issued | 2022 | |
| dc.identifier.uri | http://hdl.handle.net/10852/97824 | |
| dc.description.abstract | Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a global health threat affecting millions of people and is one of the most deadly infectious diseases. The disease is curable, but current treatment regimens are lengthy and require daily dosing of several drugs that induces adverse effects, often resulting in patient non-compliance and treatment failure. The emergence of drug resistant M. tuberculosis strains is a major problem. Treatment of drug-resistant TB is limited and currently rely on less-effective and more toxic drugs. Therefore, we need new and more effective TB-drugs that could improve or replace current treatment options.
In this thesis, I investigated the potential for enhanced TB treatment of current and experimental drugs by nanoparticle (NP) mediated delivery. The NP approach can improve the bioavailability of the drugs and enable sustained drug release and targeted delivery, resulting in increased efficacy and reduced toxicity. A selection of NPs and NP encapsulated TB-drugs where thoroughly investigated with respect to efficacy, toxicity and biodistribution using the zebrafish-TB model. Promising leads were identified and one nanoformulation progressed to testing in a mouse TB model. The screening systems and results presented can be valuable for the identification and ultimate approval of new TB-drugs. | en_US |
| dc.language.iso | en | en_US |
| dc.relation.haspart | Paper I: Zebrafish Embryos Allow Prediction of Nanoparticle Circulation Times in Mice and Facilitate Quantification of Nanoparticle–Cell Interactions. Nils-Jørgen Knudsen Dal, Agnese Kocere, Jens Wohlmann, Simon Van Herck, Tobias A. Bauer, Julien Rességuier, Shahla Bagherifam, Hilde Hyldmo, Matthias Barz, Bruno G. De Geest, and Federico Fenaroli, published in Small (2020). DOI: 10.1002/smll.201906719. The article is included in the thesis. Also available at: https://doi.org/10.1002/smll.201906719 | |
| dc.relation.haspart | Paper II: Biodistribution of surfactant-free poly(lactic-acid) nanoparticles and uptake by endothelial cells and phagocytes in zebrafish: Evidence for endothelium to macrophage transfer. Julien Rességuier, Jean-Pierre Levraud, Nils-Jørgen Knudsen Dal, Federico Fenaroli, Charlotte Primard, Jens Wohlmann, Gabrielle Carron, Gareth W. Griffiths, Dominique Le Guellec, Bernard Verrier, published in Journal of Controlled Release (2021). DOI: 10.1016/j.jconrel.2021.01.006. The article is included in the thesis. Also available at: https://doi.org/10.1016/j.jconrel.2021.01.006 | |
| dc.relation.haspart | Paper III: Rifampicin Nanoformulation Enhances Treatment of Tuberculosis in Zebrafish. Jiří Trousil, Zdeňka Syrová, Nils-Jørgen Knudsen Dal, Dmytro Rak, Rafał Konefał, Ewa Pavlova, Jana Matějková, Dušan Cmarko, Pavla Kubíčková, Oto Pavliš, Tomáš Urbánek, Marián Sedlák, Federico Fenaroli, Ivan Raška, Petr Štěpánek, Martin Hrubý, published in Biomacromolecules (2019). DOI: 10.1021/acs.biomac.9b00214. The article is not available in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1021/acs.biomac.9b00214 | |
| dc.relation.haspart | Paper IV: The zebrafish embryo as an in vivo model for screening nanoparticleformulated lipophilic anti-tuberculosis compounds. Nils-Jørgen Knudsen Dal, Martin Speth, Kerstin Johann, Matthias Barz, Claire Beauvineau, Jens Wohlmann, Federico Fenaroli, Brigitte Gicquel, Gareth Griffiths and Noelia Alonso-Rodriguez, published in Disease Models & Mechanisms (2022). DOI: 10.1242/dmm.049147. The article is included in the thesis. Also available at: https://doi.org/10.1242/dmm.049147 | |
| dc.relation.haspart | Paper V: Π-Π Interactions Stabilize PeptoMicelle-Based Formulations of Pretomanid Derivatives Leading to Promising Therapy Against Tuberculosis in Zebrafish and Mouse Models. Nils-Jørgen Knudsen Dal, Gabriela Schäfer, Andrew M. Thompson, Sascha Schmitt, Natalja Redinger, Noelia Alonso-Rodriguez, Kerstin Johann, Jessica Ojong, Jens Wohlmann, Andreas Best, Kaloian Koynov, Rudolf Zentel, Ulrich E. Schaible, Gareth Griffiths, Matthias Barz and Federico Fenaroli, manuscript submitted to Biomaterials (2022). Preprint in bioRxiv DOI: 10.1101/2022.03.10.483770. To be published. The paper is not available in DUO awaiting publishing. | |
| dc.relation.uri | https://doi.org/10.1002/smll.201906719 | |
| dc.relation.uri | https://doi.org/10.1016/j.jconrel.2021.01.006 | |
| dc.relation.uri | https://doi.org/10.1021/acs.biomac.9b00214 | |
| dc.relation.uri | https://doi.org/10.1242/dmm.049147 | |
| dc.title | Tuberculosis, Nanomedicine & the Zebrafish: Bridging the gap between in vitro and in vivo models | en_US |
| dc.type | Doctoral thesis | en_US |
| dc.creator.author | Dal, Nils-Jørgen K. | |
| dc.type.document | Doktoravhandling | en_US |