A hydrogel in combination with essential oils for oral therapy

Serra, Elisa (2018) A hydrogel in combination with essential oils for oral therapy. Doctoral thesis (PhD), Manchester Metropolitan University.

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Abstract

Oral diseases such as periodontal diseases and oral candidiasis are significant health problems in humans. Periodontal disease is a common disease of the oral cavity and the major cause of tooth loss in adults. Four clinical forms of primary oral candidiasis are recognised, and the management of such infections is limited due to the low number of antifungal drugs available, their relatively high toxicity and the emergence of antifungal resistance. The use of hydrogels in delivery of biocides has been explored due to their biocompatibility, ease with which they can be charged with drugs, and potential to confer mechanical and structural properties similar to biological tissue. This can be used both for anaerobic bacteria and fungal (i.e. Candida) infections to treat a wider spectrum of oral diseases. The aim of this study was to develop a novel antimicrobial therapy for oral diseases by utilising a hydrogel in combination with Melissa officinalis essential oil. A range of essential oils and biocides has been tested for their antifungal properties mainly against Candida albicans in a planktonic and biofilm growth form and against bacterial species associated with periodontal disease (in the planktonic growth form). The cytotoxicity of the compounds that showed the best antimicrobial properties were tested and the chosen essential oil was incorporated into a methylcellulose hydrogel. Finally, an ex vivo rodent mandible model to mimic oral candidiasis was developed. Antimicrobial screening showed Melissa officinalis to be the most successful essential oil relating to antimicrobial properties and cytotoxicity. The infection of the rodent mandible showed C. albicans invasion of the gingiva and the release of pro-inflammatory cytokines. The application of Melissa officinalis oil significantly decreased the CFU/ml and the pro-inflammatory response. One percent (1% (v/v)) and 2% (v/v) Melissa officinalis oil was successfully incorporated into 10% (w/w) and 12% (w/w) methylcellulose hydrogel. Rheology revealed that the hydrogel was injectable and gellified in two minutes at 37 °C. The drug release was a function of the Melissa officinalis concentration and the loaded hydrogel successfully inhibited Candida growth in vitro. A 3D ex vivo rodent mandible model to mimic oral candidiasis was developed and used to test the antifungal properties of Melissa officinalis oil. Moreover, a potentially injectable methylcellulose hydrogel loaded with Melissa officinalis oil was synthesised. This hydrogel was shown to elicit antifungal properties in vitro. In conclusion, the study showed that essential oils were antimicrobial and that methylcellulose hydrogels could be used as drug delivery systems.