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Title: The use of RAFT polymerisation in the synthesis of polymeric micelles for targeted drug delivery to macrophages
Author: Montgomery, Kate Shaw
ISNI:       0000 0004 7656 8209
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2016
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The aim of this project was to develop a series of polymeric micelle particles for application as selective drug delivery agents, specifically to tumour associated macrophages. In Chapter II RAFT polymerisation was applied to the synthesis of amphiphilic block copolymers and the self assembly of polymers into micelle particles was subsequently studied under aqueous conditions. Since previous studies have shown that the size of the particle is crucial for selective phagocytosis by macrophages, a series of micelles of different sizes were prepared by altering the polymer composition and chain length. The size of the particles synthesised ranged from 15 nm to nearly 200 nm. In Chapter III conditions were developed to fluorescently label the micelles with rhodamine B to allow for tracking in vitro. Crosslinking conditions were also developed to increase micelle's stability in vitro. A succinimide monomer was incorporated into the hydrophilic section of the polymer, once assembled the micelles were shell-crosslinked using a diamine linker. In Chapter IV cellular studies comparing macrophage and non-macrophage uptake were performed to determine promising candidates for selective drug delivery to macrophages. Micelles were successfully endocytosed by macrophages, however, it should be noted that micelles were also endocytosed by non-macrophage cells. Micelle size did not have an effect on endocytosis within the range tested but some micelles were endocytosed more than others. A fluorescent dye was encapsulated inside micelles so that the micelle and cargo could be independently tracked. The fluorescent dye was successfully delivered to cells. The reproducibility of results was analysed and the most promising candidate for drug delivery was identified.
Supervisor: Fuchter, Matthew Sponsor: Engineering and Physical Sciences Research Council ; Commonwealth Scientific and Industrial Research Organization (Australia)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral