title: Potential of photodynamic therapy in treatment of fungal infections of the mouth. Design and characterisation of a mucoadhesive patch containing toluidine blue O.
abstract: Mucocutaneous oropharyngeal candidiasis is predominately caused by Candida albicans. The overall incidence of oral candidiasis in young adults has increased dramatically with the spread of HIV/AIDS. Conventional treatments have been shown to have a fungistatic rather than a fungicidal effect, resulting in an inadequate treatment outcome for patients. In addition, increasing resistance of C. albicans to antifungal agents has made effective treatment more difficult. Accordingly, interest has arisen in development of new prophylaxis/treatment regimens. One such alternative treatment is photodynamic antimicrobial chemotherapy (PACT), in which a combination of a photosensitising drug and visible light cause selective destruction of microbial cells. Due to the highly coloured nature of photosensitisers and the potential for staining of teeth, lips and buccal mucosa, administration of photosensitisers to humans as a liquid mouthwash is undesirable. Targeted delivery of the photosensitiser directly to the site of infection should be the aim. The current study, therefore, reports on a mucoadhesive patch containing toluidine blue O (TBO), as a potential delivery system for use in PACT of oropharyngeal candidiasis. Patches prepared from aqueous blends of poly(methyl vinyl ether/maleic anhydride) and tripropyleneglycol methyl ether possessed suitable properties for use as mucoadhesive drug delivery systems and were capable of resisting dissolution when immersed in artificial saliva. When releasing directly into an aqueous sink, patches containing 50 and 100mg TBO cm(-2) both generated receiver compartment concentrations exceeding the concentration (2.0-5.0 mg ml(-1)) required to produce high levels of kill (>90%) of both planktonic and biofilm-grown C. albicans upon illumination. However, the concentrations of TBO in the receiver compartments separated from patches by membranes intended to mimic biofilm structures were an order of magnitude below those inducing high levels of kill, even after 6h release. Therefore, short application times of TBO-containing mucoadhesive patches should allow treatment of recently-acquired oropharyngeal candidiasis, caused solely by planktonic cells. Longer patch application times may be required for persistent disease where biofilms are implicated.
authors.affiliation: School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK. r.donnelly@qub.ac.uk
authors.forename: Ryan F
authors.initials: RF
authors.lastname: Donnelly
authors.forename: Paul A
authors.initials: PA
authors.lastname: McCarron
authors.forename: Michael M
authors.initials: MM
authors.lastname: Tunney
authors.forename: A
authors.initials: A
authors.lastname: David Woolfson
mesh_terms: D000818:Animals; D018441:Biofilms / Q000187:drug effects; D002180:Candidiasis, Oral / Q000628:therapy; D016503:Drug Delivery Systems / Q000379:methods; D009059:Mouth Diseases / Q000628:therapy*; D009061:Mouth Mucosa; D009181:Mycoses / Q000628:therapy*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D013552:Swine; D014048:Tolonium Chloride / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D017319:Photosensitizing Agents; D014048:Tolonium Chloride