Carreadores lipídicos nanoestruturados para incorporação de ftalocianina e utilização na terapia fotodinâmica

Abstract

Photodynamic therapy (PDT) is a promising, minimally invasive therapeutic modality that has low toxicity in the biological system. PDT is based on the local or systemic application of a photosensitizer (PS), which accumulates in pathological tissues. The FS molecules absorb light from an appropriate wavelength, initiating photochemical reaction processes that result in the formation of singlet oxygen (1O2) and reactive oxygen species (ROS). Currently, there are several PSs, among them, we have Phthalocyanine (PC), a second generation FS. However, one of its limitations is related to its hydrophobic nature, which can induce aggregation in biological systems with reduced photodynamic activity. The incorporation of PC in nanostructured lipid carriers (NLC) can be a promising alternative to overcome this problem. Thus, the objective of this work was to develop and characterize PC-loaded NLCs for later application in photodynamic therapy. For the development of the formulations, the fusion-emulsification technique followed by sonication was applied. The NLC and NLC-PC were characterized in terms of mean diameter (D.mn), polydispersion index (PdI), zeta potential (Pz), encapsulation efficiency (% EE), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), photobleaching and singlet oxygen generation in cell systems (SOSG). In addition, in vitro release tests were performed using the beaker method, using dialysis membranes. The average size of the NLC and NLC-PC formulations were less than 200 nm, PdI <0.3 and Pz between -15.3 ± 0.18 to -12.2 ± 0.7 and -17.8 ± 0, 54 to -19.9 ± 0.5, and stable during the storage period (90 days). Transmission electron microscopy showed spherical particles, without clusters consistent with the results of mean diameter and PdI, the NLC-PC promoted the encapsulation of 75.57% ± 0.58. DSC analysis confirmed that there was no incompatibility between PC and NLC. The analysis of the photobleaching profile proved to be photo-stable after encapsulation of NLC-PC. The study of SOSG fluorescence intensity showed production of 1O2 of the formulations after irradiation and this corroborated with the data obtained by photobleaching. The in vitro release study showed an extended release for 160 h. The formulations presented a release profile with kinetics that follows Weibull's mathematical model and zero order. The results of this work confirmed that the produced nanostructured systems are stable and promising, and could be a nanotechnological alternative for the development of new pharmaceutical forms for photodynamic therapy.