title: Using chitosan gels as a toluidine blue O delivery system for photodynamic therapy of buccal cancer: In vitro and in vivo studies.
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.
  
  
  CONCLUSIONS
  4% (w/w) CH based mucoadhesive gel can be explored as a TBO delivery system in the PDT of oral cancer.
authors.affiliation: School of Pharmacy, University of Uberaba (UNIUBE), Av. Nenê Sabino, 1801, Bairro Universitário, CEP: 38055-500, Uberaba, MG, Brazil.
authors.forename: Thierllen Barroso
authors.initials: TB
authors.lastname: Graciano
authors.affiliation: School of Pharmacy, University of Uberaba (UNIUBE), Av. Nenê Sabino, 1801, Bairro Universitário, CEP: 38055-500, Uberaba, MG, Brazil.
authors.forename: Tatielle Soares
authors.initials: TS
authors.lastname: Coutinho
authors.affiliation: School of Pharmacy, University of Uberaba (UNIUBE), Av. Nenê Sabino, 1801, Bairro Universitário, CEP: 38055-500, Uberaba, MG, Brazil.
authors.forename: Camila Beatriz
authors.initials: CB
authors.lastname: Cressoni
authors.affiliation: School of Pharmacy, University of Uberaba (UNIUBE), Av. Nenê Sabino, 1801, Bairro Universitário, CEP: 38055-500, Uberaba, MG, Brazil.
authors.forename: Cristhiane de Paula
authors.initials: Cde P
authors.lastname: Freitas
authors.affiliation: Faculty of Pharmacy, Federal University of Rio de Janeiro (UFRJ), Av. Carlos Chagas Filho, 373, CEP: 21.941.590, Rio de Janeiro, RJ, Brazil.
authors.forename: Maria Bernadete Riemma
authors.initials: MB
authors.lastname: Pierre
authors.affiliation: Laboratory of Biopathology and Molecular Biology, University of Uberaba (UNIUBE), Av. Nenê Sabino, 1801, Bairro Universitário, CEP: 38055-500, Uberaba, MG, Brazil.
authors.forename: Sanívia Aparecida de Lima
authors.initials: SA
authors.lastname: Pereira
authors.affiliation: Department of Mechanical Engineering, Federal University of Triangulo Mineiro (UFTM), Av. Frei Paulino, 30, Bairro Abadia, CEP: 38025-180, Uberaba, MG, Brazil.
authors.forename: Marcos Massao
authors.initials: MM
authors.lastname: Shimano
authors.affiliation: School of Pharmacy, University of Uberaba (UNIUBE), Av. Nenê Sabino, 1801, Bairro Universitário, CEP: 38055-500, Uberaba, MG, Brazil.
authors.forename: Renata Cristina da Cunha
authors.initials: RC
authors.lastname: Frange
authors.affiliation: School of Pharmacy, University of Uberaba (UNIUBE), Av. Nenê Sabino, 1801, Bairro Universitário, CEP: 38055-500, Uberaba, MG, Brazil; School of Pharmacy and Biochemistry, Federal University of São Paulo (UNIFESP), Campus Diadema, Rua São Nicolau, 210, CEP: 09913-030, Diadema, SP, Brazil. Electronic address: mtjgarcia@yahoo.com.
authors.forename: Maria Teresa Junqueira
authors.initials: MT
authors.lastname: Garcia
mesh_terms: D065966:Absorption, Physicochemical; D000284:Administration, Oral; D000818:Animals; D048271:Chitosan / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000138:chemical synthesis; D004058:Diffusion; D005260:Female; D005782:Gels / Q000737:chemistry*; D051379:Mice; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage; D014048:Tolonium Chloride / Q000008:administration & dosage* / Q000737:chemistry; D016896:Treatment Outcome; D014783:Viscosity
chemical_list: D003692:Delayed-Action Preparations; D005782:Gels; D017319:Photosensitizing Agents; D014048:Tolonium Chloride; D048271:Chitosan
keywords: Buccal cancer; Chitosan-based mucoadhesive gel; In vitro retention; In vivo retention; Photodynamic therapy; Toluidine blue O