Nanopartículas de sílica híbridas termossensíveis contendo doxorrubicina como um potencial sistema aplicado ao tratamento do câncer

Abstract

Cancer affects several people in the world and it is one of the diseases responsible for the main causes of death worldwide. Unfortunately, the therapies used to eliminate cancer cells also act against healthy cells, due to their low selectivity action. Inside this reality, the searches for more effective treatments that would cause less adverse effects have been encouraged, specially treatments involving the use of nanostructured carrier systems, considering their promising results. In this work, SBA-16 silica nanoparticles were synthesized and functionalized with 3-aminopropyltriethoxysilane and tests were performed on both matrices. The Fourier transform infrared spectroscopy (FTIR) technique made it possible to visualize characteristic bands of the synthesized materials such as: silane groups (Si-O-Si) and silanol groups (Si-OH) for SBA-16, ethyl group, silane groups and less intense hydroxyl band in the functionalized SBA-16 spectrum (APTES-SBA-16). The small angle X-ray scattering (SAXS) test revealed standard peaks from the samples, indicating the mesoporous and body cubic centered structure, of the Im3m spatial group. The study of adsorption and gas desorption, using Barrett-JoynerHalenda (BJH) method, showed a high surface area for SBA-16 (975 m²/g) and a significant reduction in the area of the funcionalized material (472 m²/g). The micrographs obtained by transmission electron microscopy (TEM) technique for SBA-16 and APTES-SBA-16 samples revealed a well-defined pore ordering in both matrices. The test also showed the modification of the material after functionalization, due to the use of electron energy loss spectroscopy (EELS), in which it was possible to observe the presence of nitrogen atoms in the functionalized material. Thermogravimetric analysis also helped to prove the functionalization of SBA-16 samples by the difference of mass between the samples obtained. The data showed average sizes (300 nm) on both matrices, size considered ideal for biomedical applications. After specified analysis had been made in the materials, the antitumor drug Doxorubicin was incorporated in the matrices SBA-16 and APTES-SBA-16. The rate of drug incorporation in both matrices was evaluated using high performance liquid chromatography (HPLC)7 technique with a DAD (Diode Array Detector). To quantify the drug, a calibration curve was constructed with a coefficient of determination (r2) equal to 0.993. The data obtained reveal there was an incorporation rate of 87 % for SBA-16 matrix and 29 % for APTES-SBA-16 samples. Subsequently, the functionalized silica was grafted with the thermosensitive copolymer [poli(Vinilcaprolactam) -co- (N-isopropylacrylamide)] (PVCL-co-PNIPAAm), obtaining a hybrid material that may control the drug release by means of heat. Finally, this hybrid material was characterized physically and chemically. The FTIR results revealed characteristic groups of polymers used. The dynamic light scattering (DLS) analysis showed that the sample has an average size of 447.5 nm  34 nm and a polydispersity index equal to 0.223. Such results indicate that it is a monodisperse material with an ideal size to be used as a biocarrier, due to the enhanced permeation and retention (EPR).