Using chitosan gels as a toluidine blue O delivery system for photodynamic therapy of buccal cancer: In vitro and in vivo studies

Photodiagnosis Photodyn Ther. 2015 Mar;12(1):98-107. doi: 10.1016/j.pdpdt.2014.11.003. Epub 2014 Nov 25.

Abstract

Background: Photodynamic therapy (PDT) is an emerging treatment that has demonstrated potential for the clinical treatment of buccal cancer. It is based on the photoactivation of a photosensitizer (PS) when irradiated by light at a specific wavelength. The light-excited PS generates reactive oxygen species that cause the destruction of tumor cells by apoptosis or necrosis. Toluidine Blue O (TBO) is a PS that has shown potential for PDT in cancer treatment. However, saliva and mechanical activities quickly remove the PS from the surface of the buccal mucosa. Therefore, the bioavailability of PS at the surface of target tissues is reduced. The aim of this study was to evaluate the potential of chitosan (CH) gels in TBO delivery to buccal tissue.

Methods: CH gels were obtained at different concentrations and their physico-chemical properties (pH and rheology), mucoadhesion, in vitro release profile, in vivo retention and in vivo efficacy by the ability to induce cell apoptosis were evaluated.

Results: CH-based mucoadhesive gels optimized the release and adherence of preparations at the target site. Specifically, 4% (w/w) CH gel showed adequate properties for buccal use, such as pH value, mucoadhesion, pseudoplastic behavior, extended release, minimal permeation and higher TBO retention by the mucosa. In vivo studies showed the potential of the gel to enhance TBO retention and induce cell apoptosis after laser irradiation.

Conclusion: 4% (w/w) CH based mucoadhesive gel can be explored as a TBO delivery system in the PDT of oral cancer.

Keywords: Buccal cancer; Chitosan-based mucoadhesive gel; In vitro retention; In vivo retention; Photodynamic therapy; Toluidine blue O.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption, Physicochemical
  • Administration, Oral
  • Animals
  • Chitosan / chemistry*
  • Delayed-Action Preparations / administration & dosage*
  • Delayed-Action Preparations / chemical synthesis
  • Diffusion
  • Female
  • Gels / chemistry*
  • Mice
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / pathology
  • Photochemotherapy / methods*
  • Photosensitizing Agents / administration & dosage
  • Tolonium Chloride / administration & dosage*
  • Tolonium Chloride / chemistry
  • Treatment Outcome
  • Viscosity

Substances

  • Delayed-Action Preparations
  • Gels
  • Photosensitizing Agents
  • Tolonium Chloride
  • Chitosan