Poloxamer bioadhesive hydrogel for buccal drug delivery: Cytotoxicity and trans-epithelial permeability evaluations using TR146 human buccal epithelial cell line

Int J Pharm. 2015 Nov 30;495(2):1028-37. doi: 10.1016/j.ijpharm.2015.09.045. Epub 2015 Sep 25.

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.

Keywords: Apoptosis; Buccal tolerance; Digital holographic microscopy; Necrosis; Pluronic; Xanthan gum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Buccal
  • Albuterol / administration & dosage*
  • Albuterol / chemistry
  • Albuterol / pharmacology
  • Apoptosis / drug effects
  • Cell Line
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cell Survival / drug effects
  • Drug Delivery Systems / methods*
  • Epithelial Cells / cytology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Humans
  • Hydrogel, Polyethylene Glycol Dimethacrylate / administration & dosage*
  • Hydrogel, Polyethylene Glycol Dimethacrylate / adverse effects
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry
  • Permeability
  • Poloxamer / administration & dosage*
  • Poloxamer / adverse effects
  • Poloxamer / chemistry
  • Tissue Adhesives / administration & dosage*
  • Tissue Adhesives / adverse effects
  • Tissue Adhesives / chemistry

Substances

  • Tissue Adhesives
  • Poloxamer
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Albuterol