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Title: Synthesis and characterisation of the thermoresponsive copolymers and peptide-polymer conjugates based on poly(N-isopropylacrylamide)
Author: Stoica, Florentina
ISNI:       0000 0001 3486 5289
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2008
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Responsive polymers are of great interest in biomedical applications such as tissue engineering, drug delivery and cell adhesion mediators systems. Particularly thermoresponsive polymers have been found valuable due to their ability to induce a response with the change in temperature. The prototype thermoresponsive polymer, poly(N-isopropylacrylamide) (PNIPAAm), exhibits a reversible phase transition at body temperature. Several factors can influence the phase transition of PNIPAAm including chemical structure, morphology, chemical environment and synthesis conditions. The exact relationship between these parameters and the phase transition of PNIPAAm is still poorly understood and was investigated in this research work. Similarly to thermoresponsive polymers, peptide self-assembling hydrogels are also very attractive for tissue engineering applications due to their ability to promote cell attachment. Peptide - polymer Thermoresponsive hydrogels constitute promising materials for tissue engineering due to their interior aqueous environment and their ability to release the cells at the appropriate place in response to a suitable change in temperature. New routes for synthesis of thermoresponsive hydrogels represent a challenge in the field and finding innovative ways to synthesise thermoresponsive polymer-peptide conjugates together with the understanding of their hydrogels behaviour represented the aim on this project. We have investigated the structure of a set of PNIPAAm oligopolymers with molecular weights ranging from 5000 to 11000 g morl and studied the influence of concentration, molecular weight, end groups and heating rate on the phase transition. In order to analyse the influence of the chemical composition on the phase transition, we synthesised and characterised 3 carboxyl acrylic comonomers, varying the chain length. The comonomers were used to synthesise a sets of PNIPAAm acrylic copolymers with different N-isopropylacrylamide to comonomer molar ratios 12:1,9:1 and 6:1. The structure and morphology ofpolymers was analysed by infrared spectroscopy (ATR-FTIR), nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The phase transition was examined by differential scanning calorimetry (DSC) and ultraviolet spectroscopy. The combination of these different techniques allowed us to characterise, understand and propose a mechanism of the phase transition of the PNIPAAm copolymers. Copolymers with longer chains and higher acrylic comonomer content have an increased hydrophobic content and consequently exhibit lower phase transition temperatures. Second stage of this research focused on finding new route for synthesis of peptide-polymer conjugates. For this purpose, four octopeptides (FEFKFEFK, FEFEFKFK, FEFRFEFR and FEFRFEFR) were synthesised, varying the type and the distribution of the aminoacids. The peptides were modified by a polymerisation transfer agent via solid state coupling procedure. This allowed the immobilisation of the transfer agent moiety to the amine side chain ofpeptide via amide bond formation. The structure of the peptides and the modification step were followed by matrixassisted laser desorption/ionisation (MALDI), high phase liquid chromatography (HPLC) and elemental analysis. Polymerisation of the NIPAAm in the presence of the peptide - transfer agent led to the successful formation of the conjugate. Varying the type and the content of peptide during the copolymerisation resulted in a wide range of peptide-polymer hybrid materials. The peptide polymer conjugates base on more hydrophilic peptides (FEFKFEFK and FEFEFKFK) were able to form reversible double thermoresponsive hydrogels. The structure of the new formed conjugates was confirmed by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The phase transition behaviour was analysed by differential scanning calorimetry (DSC) and the gelation properties were analysed by rheology. It was found that the solubility and gelation properties of the new materials were directly related to the structure of the peptide as well as the content of peptide used during polymerisation. The phase transition temperature of the new conjugates was constant (-32°C) but the reversibility of the thermoresponsive behaviour was slightly affected by the increased hydrophobicity of the systems.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available