M.Pharm., Faculty of Health Sciences, University of the Witwatersrand, 2011 / 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.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/11685 |
| Date | 13 July 2012 |
| Creators | Hazle, Deanne |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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