Nanopartículas termorresponsíveis de galactomanana de Delonix regia carboximetilada com poli(N-isopropilacrilamida) para liberação controlada de fármaco anticâncer

Abstract

Cancer is a disease that affects millions of people every year, the most commonly used treatment, chemotherapy, uses drugs that are toxic for both cancer cells and healthy cells, causing a series of side effects in patients undergoing treatment. The use of polymeric nanoparticles has been extensively studied as controlled and specific delivery systems for these drugs in cancer cells, in order to reduce side effects. In this work we investigated the effect of adding carboxylate groups to galactomannan extracted from Delonix regia seeds on the properties of copolymers of this derivative with poly(N-isopropylacrylamide) (PNIPAM). The copolymerization reaction was carried out by radical polymerization, using potassium persulfate as an initiator. Carboxymethylated galactomannans (GMCM), with different degrees of substitution, were used in the synthesis of the copolymers. Increasing the degree of substitution (DS) of GMCM promoted greater insertion of PNIPAM into the derivative chains. All copolymers show Critical Association Concentration (CAC) at 25 and 50 ºC. At 50 ºC, it is observed that the greater the GS, the greater the CAC, due to the increase in hydrophilicity due to the insertion of charge. The phase transition temperature of all copolymers was 35 ºC, with a sharp decrease in particle size after this phase transition temperature. A size reduction is observed for the copolymers using the GMCM compared to the uncharged galactomannan (GM) copolymer. Due to its nanoparticle size of less than 300 nm, the copolymer with the lowest degree of substitution (CP-GMCM1h, GS = 0.35) was chosen for the addition of the anticancer drug doxorubicin (DOX) via carbodiimide chemistry. The increase in DOX in the reaction system did not affect the amount of connected load. The conjugation of DOX promoted the decrease in the size of the nanoparticles and the system presents a controlled and greater release at pH 5.0 than at 7.4. As cancer cells have greater acidity than non-tumor cells, a greater release at pH 5.0 may indicate better drug release in tumor cells.