Synthesis, characterisation and cytotoxicity evaluation of novel polymeric carriers for polymer therapeutics: From free radical polymerisation to atom transfer radical polymerisation

Dieudonne, Lucile 2008. Synthesis, characterisation and cytotoxicity evaluation of novel polymeric carriers for polymer therapeutics: From free radical polymerisation to atom transfer radical polymerisation. PhD Thesis, Cardiff University.

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Abstract

Polymer therapeutics include water-soluble polymers designed as carriers for drugs, proteins or DNA. Over the last two decades, they have found increasing clinical use against cancer and other diseases. A growing number is in clinical trials or on the market. However, the polymers used so far have limitations including heterogeneity in structure, molecular weight, polydispersity, drug carrying capacity, lack of control of architecture and biodegradability of polymer backbone. Therefore, the aim of this study was to synthesise and characterise a library of linear/star homo/copolymers with potential for further development as second-generation polymer therapeutics. Atom Transfer Radical Polymerisation (ATRP) and (chain transfer agent - CTA) Free Radical Polymerisation (FRP) techniques were used to synthesise water-soluble amine-based acrylamide and methacrylate homo/copolymers. Nuclear magnetic resonance, gel permeation chromatography, infrared and titration were used for characterisation. In vitro cytotoxicity studies of the polymers towards a murine melanoma cell line were performed using a cell viability evaluating colorimetric assay. Molecular weights (from 3,000 to 550,000 g.mol --1) were successfully adjusted by varying either the initiator or CTA to monomer ratios. Semitelechelic homo/copolymers with either carboxylic acid or hydroxyl termini were obtained using mercapto-based CTA. Either stable or degradable star-shaped poly(dimethylaminoethyl methacrylate) were obtained by copper-mediated ATRP using previously synthesised multifunctional initiators (4, 5 or 8 initiating moieties). A linear increase of predictable molecular weight with monomer conversion and narrow polydispersity (1.3) were observed. Amongst other molecular parameters systematically tested, the amount of cationic residues had the most striking effect on the cell viability. To conclude, conditions were optimised for the synthesis of a library of water- soluble amine-based homo/copolymers with different molecular weight, composition, charge density and architecture using several polymerisation techniques. Preliminary evaluation of polymer cytotoxicity associated to molecular parameters is vital for intelligently designing future, novel, and biocompatible polymeric carriers.

Item Type:	Thesis (PhD)
Status:	Unpublished
Schools:	Pharmacy
Subjects:	R Medicine > RM Therapeutics. Pharmacology
ISBN:	9781303182518
Funders:	Centre for Polymer Therapeutics, Welsh School of Pharmacy, Cardiff University
Date of First Compliant Deposit:	30 March 2016
Last Modified:	12 Feb 2016 23:14
URI:	https://orca.cardiff.ac.uk/id/eprint/55722

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