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

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.

Tailoring Drug Release Properties by Gradual Changes in the Particle Engineering of Polysaccharide Chitosan Based Powders.

Chitosan is a natural copolymer generally available in pharmaceutical and food powders associated with drugs, vitamins, and nutraceuticals. This study focused on monitoring the effect of the morphology and structural features of the chitosan particles for controlling the release profile of the active pharmaceutical ingredient (API) propranolol hydrochloride. Chitosan with distinct molecular mass (low and medium) were used in the formulations as crystalline and irregular particles from commercial raw material, or as spherical, uniform, and amorphous spray-dried particles. The API⁻copolymer interactions were assessed when adding the drug before (drug-loaded particles) or after the spray drying (only mixed with blank particles). The formulations were further compared with physical mixtures of the API with chitin and microcrystalline cellulose. The scanning electron microscopy (SEM) images, surface area, particle size measurements, X-ray diffraction (XRD) analysis and drug loading have supported the drug release behavior. The statistical analysis of experimental data demonstrated that it was possible to control the drug release behavior (immediate or slow drug release) from chitosan powders using different types of particles.