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1.
Photodiagnosis Photodyn Ther ; 20: 48-54, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28838759

ABSTRACT

Photodynamic therapy (PDT) has been successfully employed in the treatment of oral cancer. Toluidine blue O (TBO) is a photosensitizer (PS) that has exhibited remarkable photocytotoxicity in a variety of tumour cells; however, its physicochemical properties, as well as the physicochemical properties of oral mucosa, prevent the drug from reaching the target site at a therapeutic concentration. The aim of this study was to evaluate the influence of Tween 80® (TW), which has shown potential as a penetration enhancer, on the mucosal retention of TBO for the PDT of oral cancer. 4% Chitosan-based mucoadhesive gels (CH gels) containing or not 5%TW were prepared (both containing 1%TBO), and their physicochemical properties (pH, rheology and mucoadhesion), TBO in vitro release profiles and TBO in vitro mucosal retention were evaluated. In vivo mucosal penetration studies of TBO followed by laser exposition were also carried out. The results showed that 4%CH gels containing 5%TW and 1%TBO have adequate mucoadhesive and rheological properties for oral mucosa use, although they present a slightly acid pH. TBO release studies showed that TW reduces TBO release, but it prolongs TBO release and increases TBO retention in the mucosa. In vivo studies showed that 4%CH gels containing 5%TW and 1%TBO cause an increase in the number of apoptotic cell, after laser exposition. In summary, 4%CH gels containing 5%TW may be a promising vehicle to optimize the penetration of TBO in oral mucosa and to improve the PDT response for the treatment of oral cancer.


Subject(s)
Gels/chemistry , Photochemotherapy/methods , Photosensitizing Agents/administration & dosage , Tolonium Chloride/administration & dosage , Adhesiveness , Animals , Chitosan/chemistry , Drug Delivery Systems/methods , Female , Hydrogen-Ion Concentration , Mice , Mouth Mucosa/metabolism , Mouth Neoplasms/drug therapy , Polysorbates/chemistry , Rheology
2.
Photodiagnosis Photodyn Ther ; 12(1): 98-107, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25463317

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.


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