Please cite this article in press as: Graciano TB, et al. Using chitosan gels as a toluidine blue O delivery system for
photodynamic therapy of buccal cancer: In vitro and in vivo studies. Photodiagnosis and Photodynamic Therapy (2014),
http://dx.doi.org/10.1016/j.pdpdt.2014.11.003
ARTICLE IN PRESS
+Model
PDPDT-606; No. of Pages 10
Photodiagnosis and Photodynamic Therapy (2014) xxx, xxx—xxx
Available online at www.sciencedirect.com
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jou rn al hom epage: www.elsevier.com/locate/pdpdt
Using chitosan gels as a toluidine blue O
delivery system for photodynamic therapy
of buccal cancer: In vitro and in vivo
studies
Thierllen Barroso Graciano
a
, Tatielle Soares Coutinho
a
,
Camila Beatriz Cressoni
a
, Cristhiane de Paula Freitas
a
,
Maria Bernadete Riemma Pierre
b
,
Sanívia Aparecida de Lima Pereira
c
, Marcos Massao Shimano
d
,
Renata Cristina da Cunha Frange
a
,
Maria Teresa Junqueira Garcia PhD
a,e,*
a
School of Pharmacy, University of Uberaba (UNIUBE), Av. Nenê Sabino, 1801, Bairro Universitário, CEP:
38055-500, Uberaba, MG, Brazil
b
Faculty of Pharmacy, Federal University of Rio de Janeiro (UFRJ), Av. Carlos Chagas Filho, 373, CEP:
21.941.590, Rio de Janeiro, RJ, Brazil
c
Laboratory of Biopathology and Molecular Biology, University of Uberaba (UNIUBE), Av. Nenê Sabino,
1801, Bairro Universitário, CEP: 38055-500, Uberaba, MG, Brazil
d
Department of Mechanical Engineering, Federal University of Triangulo Mineiro (UFTM), Av. Frei Paulino,
30, Bairro Abadia, CEP: 38025-180, Uberaba, MG, Brazil
e
School of Pharmacy and Biochemistry, Federal University of São Paulo (UNIFESP), Campus Diadema, Rua
São Nicolau, 210, CEP: 09913-030, Diadema, SP, Brazil
KEYWORDS
Chitosan-based
mucoadhesive gel;
Buccal cancer;
Photodynamic
therapy;
Toluidine blue O;
In vitro retention;
In vivo retention
Summary
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 prop-
erties (pH and rheology), mucoadhesion, in vitro release profile, in vivo retention and in vivo
efficacy by the ability to induce cell apoptosis were evaluated.
∗
Corresponding author at: Rua São Nicolau, 210, CEP: 09913-030, Diadema, SP, Brazil. Tel.: +55 11 3319 3576.
E-mail address: mtjgarcia@yahoo.com (M.T.J. Garcia).
http://dx.doi.org/10.1016/j.pdpdt.2014.11.003
1572-1000/© 2014 Elsevier B.V. All rights reserved.