Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.634972
Title: Controlled release of active compounds from a magnetic nanoparticle-vesicle aggregate nanomaterial
Author: Booth, Andrew
ISNI:       0000 0004 5353 5746
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2015
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Abstract:
Non-invasive and controlled release of bioactive compounds is an important goal in the development of drug delivery systems and novel biomaterials for tissue engineering. This project aims to exert spatio-temporal control over the release of bioactive compounds from phospholipid vesicle carriers by crosslinking them with superparamagnetic iron oxide nanoparticles to form a magnetic release nanostructure. The magnetic properties of the nanoparticles allow release to be triggered by an alternating magnetic field (AMF), which induces localised heating and “melts” the vesicle membranes. The aggregates can also be manipulated in space by a static magnetic field to create patterned materials. Incorporation of these aggregates into hydrogels has created novel responsive biomaterials. Controlled release of ascorbic acid-2-phosphate has been used to induce collagen production by chondrocytes, demonstrating an AMF triggered cellular response in vitro. The existing system has been redesigned after detailed characterisation and assessment of the performance of each component. Magnetic release has been extensively assessed using fluorescence techniques to quantify release, and optimised through the development of new silica-derived nanoparticle coatings and aggregate formulations informed by quantitative characterisation of nanoparticle functionalisation. The replacement of calcium alginate hydrogels as a 3D cell culture matrix with hyaluronic acid- based hydrogels was found to eliminate gel-induced leakage of vesicle contents and also improves the compatibility of the system with a greater range of cell types. Recently the effective encapsulation and AMF-triggered release of proteins including enzymes has been demonstrated and released enzymes have been demonstrated to retain their activity. Released trypsin was shown to retain proteolytic activity while hyaluronidase released into hyaluronan-derived hydrogels has been demonstrated to influence the rheological properties of the gel. A galactose-terminated lipid has been synthesised that enables specific targeting of the asialoglycoprotein (ASGPR) cell surface receptor receptor found in human hepatocytes, demonstrating the potential for customisation of the MNPV system to particular requirements.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.634972  DOI: Not available
Keywords: controlled release ; biomaterials ; vesicles ; liposomes ; enzymes ; magnetite ; nanoparticles ; AMF ; hydrogels ; cell culture ; tissue culture ; hyaluronidase
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