Prolonged drug delivery from a polymeric fibre device for the treatment of peridontal disease

Show simple item record Hazle, Deanne 2012-07-13T11:24:26Z 2012-07-13T11:24:26Z 2012-07-13
dc.description M.Pharm., Faculty of Health Sciences, University of the Witwatersrand, 2011 en_US
dc.description.abstract Periodontal disease describes a chronic bacterial infection affecting the gums and bone supporting the teeth. Bacteria present in plaque produce toxins, which lead to a cascade of inflammatory events that if left untreated may lead to permanent tooth loss. A periodontal pocket forms when the free gingiva moves away from the tooth surface. Periodontal disease is prevalent worldwide and has risk factors such as HIV and diabetes with possible links to socio-economic status. This places a large portion of the South African population at risk in an already burdened health care system. Scaling and root planning (SRP) forms the keystone of periodontal therapy, involving the removal of calculus and plaque. Multiple clinical trials have proved SRP leads to improved clinical outcomes. However, it often leaves behind microorganisms leading to recolonisation. Administration of pharmacological therapy is used in combination with SRP delivering one or more drugs. Subgingival treatment of periodontal disease involves the placement of a drug delivery device within the periodontal pocket releasing model drugs over a prolonged period of time. Targeted drug delivery devices have been the focus of periodontal research over the past two decades. To date there are no commercially available local drug delivery devices in South Africa for the treatment of periodontal disease. The aim of this study was to design, formulate and evaluate (in vitro) a novel polymeric fibre system to locally deliver an antimicrobial and an anti-inflammatory drug over 10 days to the periodontal pocket for the treatment of periodontal disease. The design of a flexible fibre would easily fit within the periodontal pocket evenly delivering the model drugs to the affected site. Alginate combined with glycerol was crosslinked with barium cations forming a monolithic fibre incorporating ciprofloxacin and diclofenac sodium, as the model antimicrobial and anti-inflammatory agents respectively. A 3-Factor Box-Behnken Design was employed to statistically optimise the fibres according to their tensile properties and drug release. The optimised formulation (3.14%w/v alginate, 22.54mL glycerol and 10.00w/v barium chloride) was evaluated for its drug release and hydration behaviour at pH 4 and 6.8, vibrational transitions and tensile properties as well as antimicrobial assays, characterising the in vitro behaviour of the device. The pH of the periodontal pocket varies from pH 2-9. Crosslinked alginate matrices demonstrate pH-responsive behaviour, therefore the polymeric fibre device was tested at pH 4 and 6.8. Drug release at pH 4 occurred as a result of drug diffusing through the polymeric fibres. However, at pH 6.8 the disruption of the fibre structure led to drug release as a consequence of the swelling and erosion of the matrix. Ciprofloxacin was sufficiently released from the drug-loaded fibres inhibiting growth of Escherichia coli, Enterococcus faecalis and Streptococcus mutans over 10 days. The physicomechanical and physicochemical properties were related to the degree of crosslinking, the effect of the plasticiser and the interaction of formulation components. The polymeric fibre device formed a strong yet flexible biodegradable matrix which simultaneously released an antimicrobial and anti-inflammatory agents in phosphate buffer solution pH 6.8 over 10 days. The promising in vitro results advocate for further analysis of the fibres. en_US
dc.language.iso en en_US
dc.subject.mesh Drug Delivery Systems en-US
dc.title Prolonged drug delivery from a polymeric fibre device for the treatment of peridontal disease en_US
dc.type Thesis en_US

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