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A novel self-assembled lipid-polymer hybrid system for efficient yet biocompatible gene delivery

Li, Gang; (2020) A novel self-assembled lipid-polymer hybrid system for efficient yet biocompatible gene delivery. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Lipid-polymer hybrid systems are gaining ever-increasing interest for the treatment of diseases arising from genetic mutations due to their facile synthetic protocols, being readily scalable, of low cytotoxicity, and crucially effecting gene transfer in a synergistic fashion. In the present study, a self-assembled hybrid gene delivery platform (EGCDNPs) comprised of a chitosan derivative EAGC [Ν-(2-ethylamino)-6- Ο-glycolchitosan] and a ‘helper lipid’ of DOPE (1,2-dioleoyl-sn-glycero-3- phosphoethanolamine) was prepared. This hybrid system is highly amenable to finetuning its molecular variables, such as molecular weight and ethylamino mole substitution, in order to achieve distinct in vitro and in vivo gene transfer properties. In total, three distinct gene delivery carriers were produced: E17GC43DNPs, E25GC45DNPs, and E28GC83DNPs. Regarding the influence of the ethylamino mole substitution of EAGC on the gene transfer behaviour of EGCDNPs, E25GC45DNPs (the higher level of ethylamino groups) achieved high gene transfection efficiency in in vitro cell lines, whereas E17GC43DNPs (the lower level of ethylamino groups) showed a very poor transfection performance. Concerning the molecular weight influence of EAGC on the gene transport performance of EGCDNPs, E28GC83DNPs (higher molecular weight) were more efficient with respect to firefly luciferase plasmid delivery to the healthy murine bladder in vivo as compared to E25GC45DNPs (lower molecular weight). Moreover, E28GC83DNPs could adhere to the murine bladder urothelium and even penetrate deeper into the regions of bladder lamina propria.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: A novel self-assembled lipid-polymer hybrid system for efficient yet biocompatible gene delivery
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/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
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
URI: https://discovery.ucl.ac.uk/id/eprint/10102620
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