RESUMO
This study examined the potential of iontophoresis in topical photodynamic therapy (PDT) of human invasive squamous cells carcinomas (SCC). SCC was induced in nude BALB/c mice by subcutaneous injection of A431 cells. Tumor penetration and distribution of the photosensitizer tetrasulfonated zinc phthalocyanine (ZnPcS4) was investigated after 10 and 30 min of in vivo iontophoresis of a gel containing ZnPcS4. PDT was performed immediately after iontophoresis using laser at 660 nm with a dose of irradiation of 100 J/cm(2) and irradiance of 48 mW/cm(2) while tumor growth was measured for 30 days. Iontophoresis increased ZnPcS4 penetration into tumors by 6-fold after 30 min when compared with passive delivery. Confocal microscopy analysis showed that ZnPcS4 was homogeneous distributed within deep regions of the tumor after iontophoresis. Irradiation of the tumors immediately after iontophoresis showed reduction in tumor size by more than 2-fold when compared to non-treated tumors. Iontophoretic-PDT treated tumors presented large areas of necrosis. The study concluded that iontophoretic delivery of photosensitizers could be a valuable strategy for topical PDT of invasive SCC.
Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Indóis/farmacologia , Iontoforese/métodos , Compostos Organometálicos/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Neoplasias Cutâneas/tratamento farmacológico , Animais , Transporte Biológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Indóis/metabolismo , Indóis/farmacocinética , Camundongos , Camundongos Nus , Necrose , Compostos Organometálicos/metabolismo , Compostos Organometálicos/farmacocinética , Permeabilidade , Fármacos Fotossensibilizantes/metabolismo , Fármacos Fotossensibilizantes/farmacocinética , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Given the hypothesis that microparticles can penetrate the skin barrier along the transfollicular route, this work aimed to obtain and characterise chitosan microparticles loaded with minoxidil sulphate (MXS) and to study their ability to sustain the release of the drug, attempting a further application utilising them in a targeted delivery system for the topical treatment of alopecia. Chitosan microparticles, containing different proportions of MXS/polymer, were prepared by spray drying and were characterised by yield, encapsulation efficiency, size and morphology. Microparticles selected for further studies showed high encapsulation efficiency (â¼82%), a mean diameter of 3.0 µm and a spherical morphology without porosities. When suspended in an ethanol/water solution, chitosan microparticles underwent instantaneous swelling, increasing their mean diameter by 90%. Release studies revealed that the chitosan microparticles were able to sustain about three times the release rate of MXS. This feature, combined with suitable size, confers to these microparticles the potential to target and improve topical therapy of alopecia with minoxidil.