Designing structural features of novel benznidazole-loaded cationic nanoparticles for inducing slow drug release and improvement of biological efficacy

• Published in: Materials Science & Engineering C 2017-09, Vol.78, p.978-987
• Main Authors: dos Santos-Silva, Alaine M., de Caland, Lilia B., de S. L. Oliveira, Ana Luíza C., de Araújo-Júnior, Raimundo F., Fernandes-Pedrosa, Matheus F., Cornélio, Alianda Maira, da Silva-Júnior, Arnóbio A.
• Format: Article
• Language: English
• Subjects: Atomic force microscopy; Benznidazol; Benznidazole; Biocompatibility; Biological activity; Biomedical materials; Cancer; Cationic nanoparticles; Cationic polymerization; Cell membranes; Colorectal carcinoma; Composition effects; Diffusion rate; Drug Carriers; Drug delivery systems; Drug Liberation; Drug targeting; Emulsification; Evaporation; Fourier transforms; HEK293 Cells; Humans; Infrared spectroscopy; Kidneys; Materials science; Mathematical models; Membranes; Microscopy; Nanoparticles; Nanostructured materials; Nanostructures characterization; Nitroimidazoles; Particle Size; Polycations; Polydispersity; Polymers; Polymethylmethacrylate; Reflectance; Toxicity; Zeta potential
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2017.04.053

Several polymers have been investigated for producing cationic nanocarriers due to their ability to cross biological barriers. Polycations such as copolymers of polymethylmethacrylate are highlighted due to their biocompatibility and low toxicity. The purpose of this study was to produce small and narrow-sized cationic nanoparticles able to overcome cell membranes and improve the biological activity of benznidazole (BNZ) in normal and cancer cells. The effect of composition and procedure parameters of the used emulsification-solvent evaporation method were controlled for this purpose. The experimental approach included particle size, polydispersity index, zeta potential, atomic force microscopy (AFM), attenuated total reflectance Fourier transforms infrared spectroscopy (ATR– FTIR), drug loading efficiency, and physical stability assays. Spherical and stable (over six weeks) sub 150nm cationic nanoparticles were optimized, with the encapsulation efficiency >80%. The used drug/copolymer ratio modulated the slow drug release, which was adjusted by the parabolic diffusion mathematical model. In addition, the ability of the cationic nanoparticles improve the BNZ uptake in the normal kidney cells (HEK 293) and the human colorectal cancer cells (HT 29) demonstrate that this novel BNZ-loaded cationic has great potential as a chemotherapeutic application of benznidazole. [Display omitted] •Small and narrow-sized cationic nanoparticles for benznidazole targeting against Chagas Disease.•Nanoencapsulation method optimized according physicochemical properties of nanoparticles•Spherical and stable (>6weeks) sub−150nm particles with encapsulation efficiency >80%.•Slow drug release controlled by diffusion dependent on drug/copolymer ratio•Biocompatibility demonstrated using normal kidney cells (HEK 293) and the human colorectal cancer cells (HT 29)•The nanoparticles improved the citotoxity effect of drug