Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.798940
Title: New tools for visualising nanoparticle drug delivery
Author: Vanden-Hehir, Sarah
ISNI:       0000 0004 8509 1609
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2019
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Abstract:
Encapsulating drugs in polymeric nanoparticles (NPs) is becoming increasingly popular for targeted and sustained drug delivery. NP drug delivery systems can increase the lifetime of therapeutics in vivo, they can improve safety by allowing a lower dose to be administered, and they are able to pass the blood brain barrier. Chapter 1 will discuss the anatomy of the brain, how it can be affected by multiple sclerosis (MS) and why NP drug delivery has an important part to play in treating this disease. Due to the nanoscale size of these drug delivery systems, it is challenging to image their uptake, distribution and fate in a biological environment. Raman scattering is a vibrational technique which can probe the chemical bonds in a sample, however, it is a very weak effect. Stimulated Raman scattering (SRS) is a dual laser technique which increases the observed Raman signal and has been used to image biological samples at video-rate. Intracellular contrast can be increased further by introducing spectroscopically bioorthogonal chemical labels to the NPs, which appear in the so called cell-silent region of the Raman spectrum. Previous work to image NPs with fluorescence and Raman microscopies will be discussed in Chapter 1. In this thesis, Raman spectroscopy was used to image bioorthogonally labelled polymeric NPs in in vitro cellular and ex vivo tissue models of the brain. The polymer poly(lactic acid-co-glycolic acid) (PLGA) was chosen as a biocompatible and biodegradable polymer widely used in drug delivery. Chapter 2 describes the synthesis of PLGA with both carbon-deuterium and alkyne modifications which both produce Raman peaks in the cell-silent region. The optimisation of NP synthesis from these labelled polymers by the emulsification-evaporation method is discussed in Chapter 3. In Chapter 4, the NPs synthesised from both the deuterium and alkyne analogues of PLGA were imaged with SRS in biological models of the brain. Tuning to the bioorthogonal peaks allowed imaging of the NPs without cellular background. Both NP analogues were imaged in primary rat microglia, the macrophages of the brain, and additionally the alkyne labelled NPs were imaged in ex vivo cortical mouse brain slices. Immunohistochemical analysis of these brain slices confirmed that the NPs were selectively taken up into microglia.
Supervisor: Hulme, Alison ; Brunton, Valerie ; Williams, Anna Sponsor: Biotechnology and Biological Sciences Research Council (BBSRC)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.798940  DOI: Not available
Keywords: drug delivery ; blood brain barrier ; Raman spectroscopy ; polymeric nanoparticles ; lactic acid-co-glycolic acid ; PLGA
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