Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.715076
Title: Biodegradable materials created by the controlled ring opening polymerisation of α-amino acid N-carboxyanhydrides and O-carboxyanhydrides
Author: Khuphe, Mthulisi
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2017
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Abstract:
Polymeric materials are excellent candidates for use as biomaterials. They are often employed as drug carriers to provide protection to encapsulated therapeutic molecules against premature metabolism, inactivation and clearance, and to reduce drug leakage and burst release, in vivo. Although significant progress in the medical sector has been registered, challenges still abound for the delivery of therapeutics. As such, the development of requisite nanocarriers and improvement of existing ones is crucial. NCA ROP and OCA ROP provide an alternative to solid phase peptide synthesis for the syntheses of polymeric biomaterials that have targeted applicability in drug delivery, in pharmaceuticals and in tissue engineering. This thesis demonstrates the use of controlled NCA ROPs and OCA ROPs to generate a range of novel poly(amino acid)s, poly(ester)s and hybrid materials through novel combinations of both techniques. Innovative routes to contemporary biomaterials that are presented include; employing a model therapeutic molecule, dopamine, to initiate NCA ROP, to yield amphiphilic dopamine-(peptide)-(peptoid) conjugates that self-assembled into biodegradable particles. Steglich esterification being used to graft alkyl groups from the OH-side groups of an oligo(L-serine) to yield a polymer capable of immobilising large quantities of edible vegetable oil, thus forming biodegradable organogels. NCA ROP initiated from a PEG star polymer that resulted in the generation of star-shaped hybrid polymers, which upon modification by thiol-ene click crosslinking, yielded polymers capable of forming disulphide-crosslinked hydrogels. Employing glucosamine to initiate sequential NCA ROP and OCA ROP reactions, to generate amphiphilic polymers that self-aggregated into monodisperse, glucose-presenting NPs. Oligo(L-serine), which was created by NCA ROP, being used to initiate the ROP of Phe OCA, yielding graft copolymers which self-aggregated into NPs that could be used for the controlled release of doxorubicin. The synthesis of diblock homopoly(ester)s, which could be used for the controlled release of hydrophobic chemotherapeutics, by the sequential ROP of Phe OCA and Glu(Bz) OCA, Phe OCA and Lys(Cbz) OCA, and Glu(Bz) OCA and Lys(Cbz) OCA. Collaborative initiatives led to the creation of prospective poly(amino acid)-metal-based anticancer therapeutics. In vitro biological studies and payload release studies were conducted on the materials created, to demonstrate their suitability as biomaterials. Proteolytic enzymes were used to trigger the degradation of poly(amino acid)-based materials, reduced environmental pH conditions were used to trigger the hydrolysis of poly(ester)-based materials and reductive environments were used to trigger the dissociation of disulfide-crosslinked hydrogels.
Supervisor: Thornton, Paul ; Guthrie, James Sponsor: Beit Trust ; University of Leeds
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.715076  DOI: Not available
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