Thesis
Zein-based nanoparticles for drug delivery applications
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2022
- Thesis identifier
- T16227
- Person Identifier (Local)
- 201762191
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Zein’s protein origin and hydrophobicity has raised concerns about its potential use as a delivery system in humans. To overcome this issue, it has been hypothesised that conjugating zein with polyethylene glycol (PEG) could provide steric shielding to the delivery system, thus preventing its opsonisation and increasing its half-life in the blood. The overall goal of this thesis was therefore to synthesise zein micelles conjugated with PEG and assess the possibility of using them for cancer drug delivery. First, we demonstrated that zein could be successfully conjugated with PEG and self-assembled into micelles with sizes ranging from 100 to 300 nm, depending on the molecular weight of PEG and PEG to zein ratio. In vitro studies revealed that PEGylated zein micelles could deliver a model hydrophobic substance, Nile red, into B16-F10-luc-G5 melanoma cells in a time-dependent manner, with higher cellular uptake observed when using smaller chain length PEG5K and lower PEG density. The impact of the protein corona on the uptake of PEGylated zein micelles by cancer cells and immune cells was then evaluated. PEGylation was shown to confer stealth effects to the zein micelles. The presence of human plasma did not impact the uptake of the micelles by melanoma cancer cells, regardless of PEG chain length. On the other hand, it decreased the uptake by macrophages and dendritic cells. Finally, the NanoAssemblrTM microfluidic system was exploited to generate zein nanoparticles. Continuous microfluidic approach was not the best option for manufacturing zein nanoparticles, as it resulted in low yield and drug entrapment. By contrast, zein nanoparticles with an appropriate size and improved encapsulation efficiency could be obtained using the conventional nanoprecipitation method. Overall, this thesis demonstrated that PEGylated zein micelles are highly promising delivery systems that should be further investigated for use in cancer drug delivery.
- Advisor / supervisor
- Dufès, Christine
- Resource Type
- Note
- This thesis was previously held under moratorium from 12th May 2022 until 12th May 2024.
- DOI
- Date Created
- 2021
Relações
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PDF of thesis T16227 | 2022-05-25 | Público | Baixar |