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Title: Synthesis, evaluation and optimisation of a novel polymersomal drug delivery system
Author: Martin, Chloe
ISNI:       0000 0004 7655 3883
Awarding Body: Ulster University
Current Institution: Ulster University
Date of Award: 2017
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This thesis begins with an introduction to the history of modern medicine and the biological therapeutics at the forefront of the personalised medicine crusade at present. Routes of administration and traditional formulations of drugs are discussed before moving on to discuss nanoscale delivery systems, developed in orderto aid the cellular permeation of these higher molecular weight, hydrophilic biological compounds. Chapter 2 presents the synthesis, characterisation and biological evaluation of a charge neutral (-0.095 ± 0.037 mV) polymeric drug delivery system (DDS) prepared from an amphiphilic PEGylated random co-polymer. The preparation of polymersomes (Ps) and subsequent characterisation using dynamic light scattering (DLS) revealed that the size of their hydrodynamic diameter can be tailored simply by varying the quantities and ratios of polymer in preparation. Ps were found to be capable of increasing cellular uptake ~5fold when compared with the same concentrations of free chromophore. Chapter 3 focuses on the adaptability of the previously described polymersomal system with the synthesis, characterisation and biological evaluation of six amphiphilic random co­polymers incorporating varying amounts of cholesteryl. The subsequently prepared Ps were then analysed for size (100 - 500 nm), zeta potential (-0.82 mV ± 0.2), encapsulation efficiency (~60 %), release kinetics and cellular uptake. Ps prepared from 12 % w/w cholesteryl polymer (11) displayed a ten-fold increase in cellular uptake of FITC-CM-dextran when compared to un-encapsulated drug, transcending the cellular membrane via endocytosis. Finally, Chapter 4 investigates the concept of Photochemical Internalisation (PCI) and its ability to facilitate intracellular drug release of Doxorubicin-HCL (DOX) from Ps using the photosensitiser Rose Bengal (RB). Three RB carbon derivatives (RBCDs) were synthesised with varying chain lengths (C4, 10 and 18) in orderto allow anchorage into the bi-layer of the Ps. Viability of HeLa and MCF-7 cells were shown to be reduced compared to relevant controls by ~9 and 4% respectively using PCI with Ps encapsulating DOX with RBC4 attached.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available