RESUMO
The hydrophilic character and aggregation phenomena exhibited by the photosensitizer zinc phthalocyanine tetrasulfonate (ZnPcSO(4)) make it difficult for this compound to penetrate the skin, and reduce the compound's photodynamic efficacy. A microemulsion (ME) was developed to increase the skin penetration of ZnPcSO(4) while avoiding its aggregation. Ternary phase diagrams composed of surfactants (Span® 80/Tween® 80), canola oil and a propylene glycol (PG)/water mixture (3:1) were constructed as a basis for choosing an adequate ME preparation. Rheological, electrical conductivity, dynamic light scattering and zeta potential studies were carried out to characterize the ME formulations. Monomerization of ZnPcSO(4) in the ME was determined photometrically and fluorometrically. In vitro skin penetration and retention of the compound in the skin were measured using porcine ear skin mounted on a diffusion cell apparatus. The in vivo accumulation 6h after ZnPcSO(4) application was determined fluorometrically in hairless mice skin. Confocal laser scanning microscopy was used to visualize ZnPcSO(4) distribution in the skin. A ME composed of canola oil:surfactant:PG-water at 38:47:15 (w/w/w) was chosen for ZnPcSO(4.) This was oil-in-water with internal phase diameter of 15.7±0.15nm. Spectroscopic techniques confirmed that the ME was able to keep ZnPcSO(4) in its monomeric form. In the in vitro penetration of ZnPcSO(4) in the stratum corneum (SC) and in epidermis (without stratum corneum) with dermis ([E+D]) was 33.0- and 28.0-fold higher, respectively compared to the control solution of the drug. In vivo studies, confirmed that when the ME was used as carrier, ZnPcSO(4) concentrations in the SC and [E+D] were about 1.6- and 5.6-fold higher, respectively, than controls. Visualization of ZnPcSO(4) skin penetration by confocal laser scanning microscopy confirmed that the ME increased both penetration and biodistribution of this photosensitizer in the skin.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Indóis/administração & dosagem , Compostos Organometálicos/administração & dosagem , Fotoquimioterapia , Fármacos Fotossensibilizantes/administração & dosagem , Absorção Cutânea/efeitos dos fármacos , Pele/efeitos dos fármacos , Animais , Composição de Medicamentos , Condutividade Elétrica , Emulsões , Feminino , Interações Hidrofóbicas e Hidrofílicas , Técnicas In Vitro , Indóis/farmacocinética , Luz , Camundongos , Camundongos Pelados , Microscopia Confocal , Compostos Organometálicos/farmacocinética , Fármacos Fotossensibilizantes/farmacocinética , Espalhamento de Radiação , Pele/metabolismo , Pele/ultraestrutura , Suínos , Distribuição Tecidual , ViscosidadeRESUMO
The goal of this work was to study the liquid crystalline structure of a nanodispersion delivery system intended to be used in photodynamic therapy after loading with photosensitizers (PSs) and additives such as preservatives and thickening polymers. Polarized light microscopy and light scattering were performed on a standard nanodispersion in order to determine the anisotropy of the liquid crystalline structure and the mean diameter of the nanoparticles, respectively. Small angle X-ray diffraction (SAXRD) was used to verify the influence of drug loading and additives on the liquid crystalline structure of the nanodispersions. The samples, before and after the addition of PSs and additives, were stable over 90 days, as verified by dynamic light scattering. SAXRD revealed that despite the alteration observed in some of the samples analyzed in the presence of photosensitizing drugs and additives, the hexagonal phase still remained in the crystalline phase.