Osteoarthritis (OA) is a chronic degenerative disease of the joint. Current treatments for this disease (such as glucocorticoid steroids) aim to reduce pain and increase mobility. Intra-articular injection is used in OA as treatment can be targeted to affected joints only. There is currently a lack of sustained release formulations for intra-articular injection. The aim of this thesis was to produce and characterise an injectable intra-articular drug delivery system capable of providing delivery of the steroid dexamethasone phosphate (DXMP) over 3 months. This would be an injectable hydrogel that contains drug loaded nanoparticles. Initially two systems Pluronic F127 gels and polyelectrolyte complexes between hyaluronic acid (HA) and chitosan, were investigated. The complexes between HA and chitosan were selected for the hydrogel portion of this system as they showed the greatest stability and promise in initial studies. To improve the polyelectrolyte complex properties a modified HA was synthesised. This modified polymer caused faster complex formation and produced stronger, more resilient complexes. DXMP was incorporated into poly(glycerol-adipate) (PGA) nanoparticles. A low but sufficient drug loading was achieved and particles were found to give a sustained drug release over 28 days. Nanoparticles were found to be efficiently incorporated and well retained within complexes. Nanoparticles slightly improved complex formation and properties. Composites were able to be formulated into an injectable form. Drug release from directly loaded complexes was rapid. A full release profile was not determined from composites of nanoparticle loaded complexes, however, over 60% of the loaded drug was recovered after 56 days of release study. Dexamethasone crystals were also incorporated directly into complexes to investigate the necessity of the use of nanoparticles. This gave a sustained drug release over 90 days making this system worthy of further investigation. These results highlight the different responses of these systems using drugs with different hydrophobicities.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:559673 |
| Date | January 2012 |
| Creators | Freddi, Matthew James |
| Publisher | University of Nottingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://eprints.nottingham.ac.uk/12662/ |
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