Membrane sacs, known as vesicles and liposomes have been widely used as stores for bioactive materials both in vitro and in vivo. The vesicles are biocompatible and in vitro experiments often use them in conjunction with magnetic nanoparticles. The magnetic nanoparticles allow the liposomes to be magnetically located and act as a trigger for release of the encapsulated materials. However, these magnetic vesicles or 'magnetoliposomes' as they are also known have not mananged to cross the barrier into clinical use. The work in this thesis aims to develop a novel system of magnetoliposomes for use in a biological environment. Magnetoliposomes are created from phospholipid suspensions extruded to give a spherical bilayer membrane. This membrane is doped with biotinylated lipids. These lipids are key to allowing the system to work in vitro. The magnetic nanoparticles are formed from iron and are coated with a novel synthetic linker to allow them to interact with the liposomes. When the liposomes and the nanoparticles are mixed in the presence of the protein avidin, large heirarchacal structures are formed which are stable under physiological conditions. The magnetoliposomes are held in an alginate hydrogel scaffold which acts as a support for the liposomes and as an adherent cell scaffold for tissue culture. This work demonstrates that this system can be used to encapsulate and release a range of bioactive molecules such as nickel chloride as a mimic for cytotoxic cancer drugs, ascorbic acid-2-phosphate for the upregulation of collagen production in chondrocytes and SB 431542 for the differentiation of mouse embryonic stem cells. The results shown in this work demonstrate that it is possible to use this novel linking system to create a new form of magnetoliposomes which are stable, biocompatible and easy to form and use. This work also demonstrates a strong model for possible drug delivery in vivo.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:568592 |
| Date | January 2013 |
| Creators | De Cogan, Felicity Jane |
| Contributors | Gough, Julie; Webb, Simon |
| Publisher | University of Manchester |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://www.research.manchester.ac.uk/portal/en/theses/targeted-delivery-in-vitro-from-magneticvesicle-gels(952ff942-ae4f-48e0-8bcc-1b744755a10a).html |
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