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Mucoadhesive thin films for the simultaneous delivery of microbicide and anti-inflammatory drugs in the treatment of periodontal diseases

Yee Lim, Sim, Dafydd, Mali, Ong, Jee, Ord-McDermott, Launa A., Board-Davies, Emma, Sands, Kirsty, Williams, David ORCID: https://orcid.org/0000-0002-7351-5131, Sloan, Alastair J. ORCID: https://orcid.org/0000-0002-1791-0903 and Heard, Charles M. ORCID: https://orcid.org/0000-0001-9703-9777 2020. Mucoadhesive thin films for the simultaneous delivery of microbicide and anti-inflammatory drugs in the treatment of periodontal diseases. International Journal of Pharmaceutics 573 , 118860. 10.1016/j.ijpharm.2019.118860

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Abstract

There is an unmet clinical need for new products to address the high percentage of the populous who present with periodontal diseases. Drug dose retention at the point of application would facilitate sustained release and more efficacious treatments. The aim of this study was to evaluate mucoadhesive polymeric thin films for simultaneous in situ delivery chlorhexidine and anti-inflammatory and analgesic drugs. Mucoadhesive thin films were prepared using a polymer mixture containing chlorhexidine (25 mg) ± diclofenac sodium (10 and 50 mg), and lidocaine hydrochloride (10 mg) or betamethasone dipropionate (10 and 50 mg). The films were assessed for in vitro drug release and localised tissue delivery, followed by determination of modulated prostaglandin E2 (PGE2) levels in ex vivo tissue and cytotoxicity using a HaCaT keratinocyte cell line. Antibacterial activity of the chlorhexidine/diclofenac film was determined against planktonic and biofilm bacteria associated with periodontal disease and dental plaque. Chlorhexidine release was consistently low (up to 10 % of initial loading) from all films, whereas the release of diclofenac, betamethasone and lidocaine exceeded 50 % within 30 min. The 50 mg betamethasone film released up to 4-fold more than the 10 mg film. Statistically significant reduction of PGE2 was observed in ex vivo porcine gingival tissue for films containing chlorhexidine with or without diclofenac, and betamethasone. No cytotoxicity was observed for any film, apart from 50 mg betamethasone at 24 h. Films loaded with chlorhexidine and diclofenac were inhibitory against relevant test bacteria. Between 3-6 log10 reductions in bacterial cell recovery was observed after biofilm exposure to the chlorhexidine films irrespective of the presence of the anti-inflammatory or anaesthetic. This work demonstrated that thin film formulations have the potential to simultaneously counter key causative factors in periodontal diseases, namely associated bacteria biofilm and chronic local inflammation.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Dentistry
Publisher: Elsevier
ISSN: 0378-5173
Date of First Compliant Deposit: 26 November 2019
Date of Acceptance: 6 November 2019
Last Modified: 16 Nov 2024 11:30
URI: https://orca.cardiff.ac.uk/id/eprint/127159

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