title: Poloxamer bioadhesive hydrogel for buccal drug delivery: Cytotoxicity and trans-epithelial permeability evaluations using TR146 human buccal epithelial cell line.
abstract: A salbutamol sulfate (SS)-Poloxamer bioadhesive hydrogel specially developed for buccal administration was investigated by studying interactions with TR146 human buccal epithelium cells (i.e. cellular toxicity (i) and trans-epithelial SS diffusion (ii)). The assessment of cell viability (MTT, Alamar Blue), membrane integrity (Neutral Red), and apoptosis assay (Hoechst 33342), were performed and associated to Digital Holographic Microscopy analysis. After the treatment of 2h, SS solution induced drastic cellular alterations that were prevented by hydrogels in relation with the concentrations of poloxamer and xanthan gum. The formulation containing P407 19%/P188 1%/Satiaxane 0.1% showed the best tolerance after single and multiple administrations and significantly reduced the trans-epithelial permeability from 5.00±0.29 (×10(3)) (SS solution) to 1.83±0.22 cm/h. Digital Holographic Microscopy images in good agreement with the viability data confirmed the great interest of this direct technique. In conclusion, the proposed hydrogels represent a safe and efficient buccal drug delivery platform.
authors.affiliation: CNRS UMR 8258-Inserm U1022, Paris Descartes University, Chimie-Paris Tech, 4, avenue de l'observatoire, F-75006 Paris, France; Unither Pharmaceuticals-Unither Développement Bordeaux, ZA Tech Espace, Av. Toussaint Catros, F-33185 Le Haillan, France.
authors.forename: Ni
authors.initials: N
authors.lastname: Zeng
authors.affiliation: CNRS UMR 8258-Inserm U1022, Paris Descartes University, Chimie-Paris Tech, 4, avenue de l'observatoire, F-75006 Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Mignet
authors.affiliation: CNRS UMR 8258-Inserm U1022, Paris Descartes University, Chimie-Paris Tech, 4, avenue de l'observatoire, F-75006 Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Dumortier
authors.affiliation: UMR 8638CNRS COMETE, Paris Descartes University, 4, avenue de l'observatoire, F-75006 Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Olivier
authors.affiliation: CNRS UMR 8258-Inserm U1022, Paris Descartes University, Chimie-Paris Tech, 4, avenue de l'observatoire, F-75006 Paris, France.
authors.forename: Johanne
authors.initials: J
authors.lastname: Seguin
authors.affiliation: Unither Pharmaceuticals-Unither Développement Bordeaux, ZA Tech Espace, Av. Toussaint Catros, F-33185 Le Haillan, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Maury
authors.affiliation: CNRS UMR 8258-Inserm U1022, Paris Descartes University, Chimie-Paris Tech, 4, avenue de l'observatoire, F-75006 Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Scherman
authors.affiliation: UMR 8638CNRS COMETE, Paris Descartes University, 4, avenue de l'observatoire, F-75006 Paris, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Rat
authors.affiliation: CNRS UMR 8258-Inserm U1022, Paris Descartes University, Chimie-Paris Tech, 4, avenue de l'observatoire, F-75006 Paris, France; Mise au point galénique, Agence Générale des Equipements et des Produits de Santé (AGEPS), AP-HP, 7, rue du fer à moulin, F-75005 Paris, France. Electronic address: vincent.boudy@eps.aphp.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: Boudy
mesh_terms: D000278:Administration, Buccal; D000420:Albuterol / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D010539:Permeability; D020442:Poloxamer / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D014014:Tissue Adhesives / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry
chemical_list: D014014:Tissue Adhesives; D020442:Poloxamer; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D000420:Albuterol
keywords: Apoptosis; Buccal tolerance; Digital holographic microscopy; Necrosis; Pluronic; Xanthan gum