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Mucoadhesive Poloxamer-Based Hydrogels for the Release of HP-beta-CD-Complexed Dexamethasone in the Treatment of Buccal Diseases

Abstract : Oral lichen planus (OLP) is an ongoing and chronic inflammatory disease affecting the mucous membrane of the oral cavity. Currently, the treatment of choice consists in the direct application into the buccal cavity of semisolid formulations containing a corticosteroid molecule to decrease inflammatory signs and symptoms. However, this administration route has shown various disadvantages limiting its clinical use and efficacy. Indeed, the frequency of application and the incorrect use of the preparation may lead to a poor efficacy and limit the treatment compliance. Furthermore, the saliva clearance and the mechanical stress present in the buccal cavity also involve a decrease in the mucosal exposure to the drug. In this context, the design of a new pharmaceutical formulation, containing a steroidal anti-inflammatory, mucoadhesive, sprayable and exhibiting a sustained and controlled release seems to be suitable to overcome the main limitations of the existing pharmaceutical dosage forms. The present work reports the formulation, optimization and evaluation of the mucoadhesive and release properties of a poloxamer 407 thermosensitive hydrogel containing a poorly water-soluble corticosteroid, dexamethasone acetate (DMA), threaded into hydroxypropyl-beta-cyclodextrin (HP-beta-CD) molecules. Firstly, physicochemical properties were assessed to ensure suitable complexation of DMA into HP-beta-CD cavities. Then, rheological properties, in the presence and absence of various mucoadhesive agents, were determined and optimized. The hydration ratio (0.218-0.191), the poloxamer 407 (15-17 wt%) percentage and liquid-cyclodextrin state were optimized as a function of the gelation transition temperature, viscoelastic behavior and dynamic flow viscosity. Deformation and resistance properties were evaluated in the presence of various mucoadhesive compounds, being the sodium alginate and xanthan gum the most suitable to improve adhesion and mucoadhesion properties. Xanthan gum was shown as the best agent prolonging the hydrogel retention time up to 45 min. Furthermore, xanthan gum has been found as a relevant polymer matrix controlling drug release by diffusion and swelling processes in order to achieve therapeutic concentration for prolonged periods of time.
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https://hal-cnrs.archives-ouvertes.fr/hal-03291063
Contributor : Colette Orange <>
Submitted on : Monday, July 19, 2021 - 4:10:34 PM
Last modification on : Friday, July 23, 2021 - 3:53:02 AM

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Raul Diaz-Salmeron, Balthazar Toussaint, Nicolas Huang, Etienne Bourgeois Ducournau, Gabriel Alviset, et al.. Mucoadhesive Poloxamer-Based Hydrogels for the Release of HP-beta-CD-Complexed Dexamethasone in the Treatment of Buccal Diseases. Pharmaceutics, MDPI, 2021, 13 (1), ⟨10.3390/pharmaceutics13010117⟩. ⟨hal-03291063⟩

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