Investigating liposomes for local drug delivery in spinal cord injury (SCI)

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dc.contributor.advisor O'Carroll, S en Newland, Julia en 2019-02-07T03:29:38Z en 2018 en
dc.identifier.uri en
dc.description Full Text is available to authenticated members of The University of Auckland only. en
dc.description.abstract Spinal cord injury (SCI) is a devastating issue that affects many people worldwide. In New Zealand, SCI effects up to 170 people annually and is largely caused by motor vehicle accidents, falls and sports injuries. SCI evolves over three phases, the primary injury, secondary injury and chronic injury. The symptoms of a SCI typically include motor dysfunction and neuropathic pain which not only affects the patient but also the family and instigates a cascade of economic and emotional distress. Current treatment involves the mitigation of symptoms but does not cure the SCI. Depending on the severity of the SCI, treatment can include surgical intervention which is often invasive or by administering drugs. The current choice for drug administration is orally, which is convenient for the patient. However, using a systemic system for delivery of drugs can pose challenges due to unspecific delivery of drug and malabsorption by the gut. This project investigated the use of hyaluronic acid (HA, a ligand of Cluster of differentiation-44 or CD44) tagged liposomes as a method of local delivery to the area of trauma. We investigated spinal cord injury (SCI) 1, 3, 7, 10 and 14 days after trauma. These were chosen as a range of time points for investigating spinal cord injury. These time points were also based on the literature for when the blood spinal cord barrier (BSCB) was demonstrated to have increased CD44 levels and is leaky. Immuno-labelling for CD44 is upregulated under inflammation demonstrated the levels of CD44 seen across the chosen time points. Immuno-labelling for fibrinogen, a marker demonstrated the leakiness of the BSCB. This is demonstrated over a series of time points post SCI. Based on the results of our CD44 and fibrinogen labelling, 1 and 7 days post SCI were selected as time points to deliver liposomes. To test our local treatment for SCI, HA tagged and non-HA tagged liposomes labelled with the fluorophore rhodamine were injected by tail vain to see if they effectively targeted the injury area. Spinal cord tissue was immuno-labelled with the markers GFAP, CD44 or CD68 to evaluate the co-localisation with liposomes. The results of our CD44 and fibrinogen DAB staining showed that maximal staining was seen 1 day post SCI, inferring that there is maximum inflammation and BSCB leakage seen 1 day post SCI. Our co-localisation experiments show that liposomes appeared to co-localise with CD44 and CD68 in the spinal cord tissue 1 and 7 days post SCI. There was co-localisation seen with GFAP in the spinal cord. Further analysis showed that liposomes appeared to be broken down and metabolised by the spleen, liver and kidney. Our project aimed to establish a type of treatment which can be delivered locally to SCI. en
dc.publisher ResearchSpace@Auckland en
dc.relation.ispartof Masters Thesis - University of Auckland en
dc.relation.isreferencedby UoA99265119913002091 en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights Restricted Item. Full Text is available to authenticated members of The University of Auckland only. en
dc.rights.uri en
dc.rights.uri en
dc.title Investigating liposomes for local drug delivery in spinal cord injury (SCI) en
dc.type Thesis en Biomedical Science en The University of Auckland en Masters en
dc.rights.holder Copyright: The author en
pubs.elements-id 761079 en
pubs.record-created-at-source-date 2019-02-07 en

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