TARGETED DELIVERY IN VITRO FROM MAGNETICVESICLE GELS

Abstract

Membrane sacs, known as vesicles and liposomes have been widely used as storesfor bioactive materials both in vitro and in vivo. The vesicles are biocompatible andin vitro experiments often use them in conjunction with magnetic nanoparticles. Themagnetic nanoparticles allow the liposomes to be magnetically located and act as atrigger for release of the encapsulated materials. However, these magnetic vesicles or'magnetoliposomes' as they are also known have not mananged to cross the barrierinto clinical use. The work in this thesis aims to develop a novel system ofmagnetoliposomes for use in a biological environment.Magnetoliposomes are created from phospholipid suspensions extruded to give aspherical bilayer membrane. This membrane is doped with biotinylated lipids. Theselipids are key to allowing the system to work in vitro. The magnetic nanoparticlesare formed from iron and are coated with a novel synthetic linker to allow them tointeract with the liposomes. When the liposomes and the nanoparticles are mixed inthe presence of the protein avidin, large heirarchacal structures are formed which aerstable under physiological conditions.The magnetoliposomes are held in an alginate hydrogel scaffold which acts as asupport for the liposomes and as an adherent cell scaffold for tissue culture. Thiswork demonstrates that this system can be used to encapsulate and release a range ofbioactive molecules such as nickel chloride as a mimic for cytotoxic cancer drugs,ascorbic acid-2-phosphate for the upregulation of collagen production inchondrocytes 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 novellinking system to create a new form of magnetoliposomes which are stable,biocompatible and easy to form and use. This work also demonstrates a strong modelfor possible drug delivery in vivo.

Date of Award	1 Aug 2013
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Simon Webb (Supervisor) & Julie Gough (Supervisor)