Estudos das propriedades físico-químicas e fotodinâmicas da ftalocianina de alumínio cloro (AIPcCI) em sistemas homogêneos e encapsulada em copolímeros micelares plurônicos® P-123 e F-127

Abstract

Photodynamic therapy (PDT) is a relatively new medical modality whose basic principle is the interaction between a photosensitive compound (photosensitizer, PS), light and molecular oxygen generating singlet oxygen and/or reactive oxygen species (ROS), which cause destruction cell. Phthalocyanines are a class of compounds which possess favorable characteristics for use as photosensitizing compounds. However, the molecules of this class such as, for example, aluminum phthalocyanine chloride (AlPcCl) have the disadvantage of suffering the process of self-aggregation in an aqueous medium, an effect that causes drastic changes in photophysical properties important FS invalidating their use in photodynamic therapy. However, the use of solubilizing systems/carriers minimizes this problem. Thus, in this work, we studied the physicochemical properties between AlPcCl copolymers and micellar Pluronic® P-123 and F-127, to obtain formulations that can be applied in PDT and photodynamic inactivation of microorganisms (PDI). Initially, studies were performed in homogeneous with AlPcCl in solvents with different polarities (water, ethanol, acetone and DMSO) calculating the coefficient of molar absorptivity (?) of the main absorption bands of AlPcCl (Soret, QI, QII and QIII), aiming to understand the spectroscopic properties and also obtain the best solvent for studies involving the encapsulation of the FS. The AlPcCl presented soluble in ethanol, suffering minimal effect of self-aggregation as there is a lower solubility and more drastic formation of self-aggregates in acetone, dimethyl sulfoxide (DMSO), chloroform, and especially in water. Additionally, the hydrophobic FS showed reasonable values of fluorescence quantum yield and singlet oxygen in ethanol, showing it feasible for application in PDT and IFDMO, being necessary to the encapsulation in this monomeric form in a solubilizer/suitable system carrier. Initial studies involving the primary interaction between the AlPcCl with F-127 and P-123 (binding isotherms), showed a profile involving complex interaction between this PS and the copolymers, probably due to complex profiles of structural organization (monomeric/self ?aggregate forms). These studies also showed a greater interaction between AlPcCl and copolymer P-123 compared to F-127. The kinetics of interaction between AlPcCl and copolymers, corroborated with the results obtained from the isotherms, showing greater interaction between AlPcCl and P-123, in addition to further stabilize AlPcCl this copolymer, including presenting a lower level of aggregation at higher concentrations of P-123 (lowest ratios [AlPcCl]/[P-123mic]). After these results involving the complex primary interaction AlPcCl/copolymers, became for the encapsulation of AlPcCl in this copolymers, using the method of solid dispersion. In formulated obtained by this method, it was found that the AlPcCl is incorporated successfully in the copolymer. However, while AlPcCl is incorporated in a self-aggregated form in F-127, in the copolymer P-123 was verified that this PS can be incorporated in the monomeric form depending on the concentration of P-123 or the ratio [AlPcCl]/[P-123mic]. This higher interaction between the AlPcCl and the copolymer P-123, observed in previous studies and also in AlPcCl encapsulated by the method of solid dispersion is due to differences in the degree of hydrophobicity between copolymers, in which the P-123 has a relatively greater amount of sites hydrophobic better able to stabilize the AlPcCl in monomeric form. Additionally, the formulation of monomeric AlPcCl in P-123 remained stable for a long period of time, maintaining their main spectroscopic properties after the lyophilization/ rehydration. The formulated the AlPcCl encapsulated in P-123 also showed promising results in studies involving photodynamic inactivation in vitro against bacteria S. aureus as well the fungus C. albicans, showing no toxicity in the dark, being feasible for application in PDI and future studies involving PDT