6 research outputs found
Terapia fotodinâmica com ftalocianina de zinco tópica: avaliação da intensidade de fluorescência, absorção cutânea, alterações histológicas e imuno-histoquÃmicas na pele do modelo animal Topical photodynamic therapy with zinc phthalocyanine: evaluation of fluorescence intensity, skin absorption, skin histological and immunohistochemical changes in animal model
FUNDAMENTOS - Ftalocianinas são promissores agentes fotossensibilizadores na terapia fotodinâmica (TFD). OBJETIVOS - Avaliar intervalos, veÃculos e a incorporação de promotor de absorção na formulação tópica da ftalocianina de zinco (FC-Zn). Avaliar alterações macro e micromorfológicas e a expressão de Fas promovidas pela TFD com FC-Zn tópica no modelo murino. MÉTODOS - Por meio da espectrometria de fluorescência, foram avaliadas combinações de diferentes perÃodos de oclusão tópica das formulações gel ou emulsão de FC-Zn (1mg/dl), com ou sem monoleÃna 5%, no dorso do camundongo hairless. Após oito horas das diferentes formulações, os camundongos foram expostos ao laser de diodo de 670nm, dose de 50J/cm-². RESULTADOS - A fluorescência foi discretamente superior após oito horas e com a emulsão nos intervalos de uma, duas e quatro horas de oclusão. A intensidade do edema e da erosão correspondeu à necrose da epiderme e à imunoexpressão de Fas nos cortes histológicos de pele. CONCLUSÕES - Os achados indicam a ação fotodinâmica promovida pela interação entre FC-Zn e fonte de luz de 670nm. As alterações macro e micromorfológicas foram correspondentes e mais substanciais com a emulsão FC-Zn e monoleÃna, sugerindo a acentuação dos efeitos com essa formulação. A imunoexpressão de Fas e as alterações histológicas sugeriram a apoptose como mecanismo de morte celular na TFD com FC-Zn tópica.<br>BACKGROUND - Phthalocyanines are promising photosensitizers used in photodynamic therapy (PDT). OBJECTIVES - To evaluate the following parameters: intervals, vehicles and enhancer using topical zinc-phthalocyanine (Zn-PC) formulation. To examine macro and micromorphological changes and Fas expression induced by topical Zn-PC-PDT on murine skin. MATERIAL AND METHODS - Using fluorescence spectrometry, different intervals of topical occlusion employing Zn-PC gel or emulsion, with or without monolein 5% were studied. After an 8-hour occlusion of different formulations, the mice were exposed to 670 nm laser, at a 50 J.cm-² dose. RESULTS - Fluorescence was slightly higher after 8 hours, and also with emulsion formulation at one-, two- and four-hour occlusion periods. The intensity of edema and erosion were correlated to epidermal necrosis and to Fas immunoexpression in skin histological specimens. CONCLUSIONS - The results show the effects of photodynamic action promoted by the interaction between Zn-PC formulation and a 670-nm light source. Macro and micromorphological alterations were correlated and more substantial with monolein and Zn-PC emulsion, suggesting more marked effects with this formulation. The Fas immunoexpression and histological changes suggested that apoptosis plays a role in the mechanism of cell death caused by PDT based in Zn-PC
Photodynamic therapy for cancer: principles, clinical applications and nano technological approaches
Photodynamic therapy (PDT) is a clinically approved, minimally
invasive procedure that can exert a cytotoxic activity toward malignant
cells. The procedure involves administration of a photosensitizer (PS)
followed by irradiation with light at wavelengths within of the PS
absorption band. In the presence of oxygen, a series of events lead to
direct tumor cell death, damage to the microvasculature, and induction
of a local inflammatory reaction. Clinical studies reveal that PDT can
be curative, particularly in early stage tumors, can prolong survival in
patients with inoperable cancers, and can significantly improve quality of
life. Unfortunately, most PS lack specificity for tumor cells and this can
result in undesirable side effects in healthy tissues. Furthermore, due to
their mostly planar structure, PS form aggregates with low photoactivity
in an aqueous environment.
Nanotechnology offers a great opportunity in PDT based on the concept
that a nanocarrier can drive therapeutic concentrations of PS to the tumor
cells without generating any harmful effect in vivo. Currently, several
nanoscale carriers made of different materials such as lipids, polymers,
metals, and inorganic materials have been proposed in nano-PDT. Each
type of system highlights pros and cons and should be selected on the
basis of delivery requirements.
In the following, we describe the principle of PDT and its application in
the treatment of cancer. Then, we illustrate the main systems proposed
for nano-PDT that demonstrated potential in preclinical models together
with emerging concepts for their advanced design