Nanoparticles of mesoporous silica functionalized with biodegradable polymers applied as carriers of Benznidazole for the treatment of Chagas disease

Synthesis of mesoporous silica nanoparticles has been intensively investigated because of its wide application range as carriers of drugs for the treatment of various diseases. In this work, the MCM-41 mesoporous silica nanoparticle was synthesized and chemically functionalized with 3-aminopropyltriethoxysilane (APTES), which acts as a crosslinker for the polymer Poly-epsilon-Caprolactone and is chemically functionalized with 3-glycidyloxypropyltrimethoxysilane (GPTMS), which acts as a crosslinker for the polymer Chitosan. After functionalization, benznidazole (BZ) was incorporated into the MCM-41 nanoparticles. BZ is the drug used in the treatment of Chagas' disease, presenting a limited efficacy and causing serious adverse effects. Chagas disease is a public health problem, affects millions of people around the world and causes high rates of morbidity and mortality in affected populations. The functional groups from the functionalization and incorporation of BZ into the MCM-41 nanoparticles were analyzed and characterized by FTIR, BET, Zeta potential, TGA, CHN, XRD, SAXS, MET, MEV, DFT, XPS and by solid state NMR of ²⁹Si, evidencing the anchoring of the organic chains on the silica surface, and ¹³C, evidencing the presence of the aminopropyl and glycidiopropyl groups during the different stages of functionalization. Results of in vitro biocompatibility assays in fibroblasts and HeLa cells indicated that MCM-41 nanoparticles have low cytotoxicity and excellent cell viability. These results have encouraged further studies on the trypanocidal effect of MCM-41 nanoparticles on the epimastigote forms of T. cruzi CLBrener strain and compare to the effect of BZ as well as suggest the mechanism of death. The BZ incorporated in the MCM-41 nanoparticles presented a good trypanocidal effect on the epimastigote forms of the T. cruzi CLBrener strain, being this effect more powerful and faster than that observed for BZ in its free form. The treatments promoted cellular alterations indicative of necrosis involving mitochondrial damage, thus demonstrating the controlled release of drugs by mesoporous silica nanoparticles MCM-41. Thus, an efficient tool to potentiate the therapeutic effect of non-selective drugs is shown, demonstrated by an excellent efficiency in the controlled and directed release of pharmacological molecules, besides presenting desirable properties, such as good biocompatibility and biodegradability. The data of the present work may be useful for the development of new nanoplatforms and for the investigation of the in vivo effects of the MCM-41 nanoparticle in the context of treatment of neglected diseases. (author)