University of Surrey

Test tubes in the lab Research in the ATI Dance Research

The development of methods for the facile synthesis of therapeutic polymer nanocarriers.

Bromley, Adam (2019) The development of methods for the facile synthesis of therapeutic polymer nanocarriers. Doctoral thesis, University of Surrey.

Adam Bromley - The Development of Methods for the Facile Synthesis of Therapeutic Polymer Nanocarriers.pdf - Version of Record
Available under License Creative Commons Attribution Share Alike.

Download (3MB) | Preview


The work in this thesis considers the development and optimisation of methods with regards to the synthesis and formation of polymeric nanomaterials. A particular focus is placed on synthesising polymers based on N-2-hydroxypropyl methacrylamide (HPMA) and ε-caprolactone (PCL) with regards to drug delivery applications. Polyethylene glycol (PEG) and PEG-based materials were intentionally avoided due to the growing body of research surrounding the accelerated blood clearance phenomenon. Reversible addition-fragmentation chain transfer (RAFT) polymerisation was employed in the synthesis of linear, block and branched forms of poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA). Linear PHPMA was synthesised according to established synthetic methods and found to yield well defined materials (12 – 17 kg mol-1; Ð 1.02 – 1.08). Homotelechelic PCL with terminal RAFT functionalities was employed as a macro-CTA in the synthesis of PHPMA-b-PCL-b-PHPMA triblock copolymers. After optimisation of the reaction conditions a reasonably well-defined amphiphilic polymer was obtained (Mn 29 kg mol-1; Ð 1.41) which was observed to undergo spontaneous self-assembly in water (average particle diameter 44 nm). Alternative synthetic routes utilising click methodologies (thiol-ene, hetero-Diels-Alder and copper azide-alkyne cycloaddition) were investigated but ultimately did not yield any improvements when compared to the macro-CTA grafting-from approach. Hyperbranched PHPMA was synthesised by a free-radical crosslinking copolymerisation method which utilised ethylene glycol dimethacrylate (EGDMA) as a divinyl crosslinking agent. Extensive characterisation of branching parameters was performed using a combination of triple detection size-exclusion chromatography (SEC) and 1H NMR. After optimising the reaction conditions, three hyperbranched copolymers of HPMA and acetylated-HPMA (APMA) were synthesised; surface RAFT moieties underwent additional polymerisation with HPMA to ultimately yield novel PHPMA-star-(hb-PHPMA-co¬-PAPMA) core-crosslinked amphiphilic star copolymers (Mn 139 – 243 kg mol-1, Ð 1.07 – 1.27). Additionally, charge controlled nanoprecipitation of homotelechelic carboxyl terminated PCLs in a range of alkaline pH buffered solutions was performed according to a literature procedure. The lowest diameter particles were observed to form when precipitation was performed in a pH 9 aqueous phase (14 ± 1 nm), as determined by dynamic light scattering (DLS). Overall, synthesis of PHPMA-b-PCL-b-PHPMA block copolymer at higher molecular weight and lower dispersity than previously reported materials from a homotelechelic dithiobenzoate macro-CTA was achieved. Furthermore, three novel PHPMA-star-(hb-(PHPMA-co-PAPMA)) copolymers were synthesised and the branching parameters of the hydrophobic core characterised by 1H NMR spectroscopy. Preliminary work into developing a scalable synthetic procedure for producing PCL nanoparticles was undertaken. Under optimal conditions PCL-oTHPA nanoparticles were produced with a number-average particle diameter of 14 ± 1 nm (error is ± 1 S.D.).

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors : Bromley, Adam
Date : 28 June 2019
Funders : British Heart Foundation
DOI : 10.15126/thesis.00851932
Contributors :
Depositing User : Adam Bromley
Date Deposited : 03 Jul 2019 08:34
Last Modified : 03 Jul 2019 08:35

Actions (login required)

View Item View Item


Downloads per month over past year

Information about this web site

© The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.
+44 (0)1483 300800