Nanoparticle design for drug delivery to atherosclerotic plaques

Student thesis: Doctoral Thesis

Abstract

Cardiovascular disease remains the main cause of death worldwide, and at the core of most cardiac problems is atherosclerosis. This progressive condition is characterised by the hardening and narrowing of the arteries. Often a cholesterol-lowering drug known as a statin is prescribed. Studies have shown these drugs to have many advantageous properties including an anti-inflammatory effect, the ability to improve endothelial function and the power to stabilise plaques. It was hypothesised that delivering the statin to the plaque could enhance these therapeutic effects since the disease is triggered from a local, rather than systemic, event.Research focussed around the drug carrier design, with initial effort to investigate potential particles for the core. Nobel metal nanoparticles, such as gold and silver, are widely studied for use in medicine, owing to their plasmon resonance and facile surface chemistry. It is their interaction with light that makes the nanoparticles trackable via surface enhanced Raman spectroscopy (SERS) and capable of exchanging light to heat. In the literature, studies have shown that the heat generated during plasmonic interrogation can trigger drug release and hence could facilitate localised statin delivery. All these properties make metallic nanoparticles an appealing candidate for the core of the drug delivery design.Iron oxide nanoparticles were synthesised and characterised as an initial vector for a drug carrier design. It was anticipated that a thin gold coating would facilitate the ability to functionalise and track the particles in vivo. As an alternative approach, hollow gold nanoparticles were investigated as the core nanoparticle, with their vacant centre allowing for higher drug payloads. Their synthesis, photothermal properties and enhancement of Raman scattering was investigated. An interesting relationship between the Raman signal and the plasmonic heating of the nanoparticles was observed. This phenomenon is not currently published in the literature, and this research theorises that an increase in 'adatom' density causes the signal enhancement.This project validated a nanoparticle vehicle for the localised delivery of statins to atherosclerotic plaques. The combination of metallic nanoparticles with SERS was studied to better understand the possibility of such a treatment.
Date of Award20 Mar 2020
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsUniversity of Strathclyde
SupervisorDuncan Graham (Supervisor) & Karen Faulds (Supervisor)

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