Encapsulamento de complexos de Au III derivados de tiossemicarbazonas para liberação controlada no tratamento da doença de Chagas

Abstract

The development of coordination compounds containing the AuIII metal center has been gaining prominence in the area of Medicinal Chemistry. Recently, the NDCBio research group reported two AuIII complexes containing the thiosemicarbazone ligand class as new promising agents for the treatment of Chagas' disease, [AuCl(L1)] and [Au(Hdamp)(L14)])Cl∙H2O. In the present work, nanoparticles (NPs) of poly (lactic-co-glycolic acid) (PLGA) have been prepared as delivery systems for both complexes through the emulsification and solvent evaporation technique. The obtained results revealed encapsulation efficiencies (EE%) determined by indirect method close to 90 % for [AuCl(L1)] and 99.7% for [Au(Hdamp)(L14)]Cl∙H2O, with NPs/[AuCl(L1)] size in the 270-280 nm range and polydispersity index (PDI) close to 0.150, while the NPs/[Au(Hdamp)(L14)]Cl∙H2O were in the 298.3 – 300.5 nm range with PDI close to 0.400. After the encapsulation process, the Zeta potential of the nanoparticles of both complexes increased in relation to NPs containing only PLGA (from -20 mV to the range of -6 to 3 mV). In addition, the [AuCl(L1)] release curve was determined and studied by mathematical models, being the Korsmeyer-Peppas model the one that best fitted to the experimental data, with R2 = 0.9199 for the lyophilized formulation and R2 = 0.97864 for the suspension formulation. Thus, it was possible to identify the release mechanism of the complex from the polymeric matrix as being through diffusion and relaxation of the polymeric chain. For the [Au(Hdamp)(L14)]Cl∙H2O complex it was not possible to get a suitable receptor medium to perform the release curve. Additionally, by means of the high resolution images obtained by SEM, it could be observed that the nanoparticulate systems of both complexes produced spherical particles with average sizes close to those analyzed by the DLS technique. By means of in vivo biological assays with Balb/C mice infected with T. cruzi parasites, it was pointed out that [Au(Hdamp)(L14)]Cl∙ּH2O was not released from the polymer matrix, since there was no desired effect during the treatment. On the other hand, the in vivo tests using the NPs/[AuCl(L1)] showed that the encapsulated complex is more efficient than the free complex, obtaining a parasitemia reduction of 55 % in relation to the control on the seventh day of treatment, in addition to a longer mice survival.