Benznidazole polymeric nanoparticles for the optimization of Chagas disease treatment

SEREMETA, K.; OKULIK, N.; SALOMON, C.

CABA

Congreso; 4th Scientific Meeting of ResNet NPND; 2018

Facultad de Farmacia y Bioquímica - Universidad de Buenos Aires

Chagas disease is a neglected disease which is caused by the parasite Trypanosoma cruzi affecting about 6 to 7 million people worldwide. Benznidazole (BNZ) is the drug of choice for the treatment of this disease, however, it exhibits low aqueous solubility limiting their dissolution and oral bioavailabilit. Thus,several strategies have been used to improve the solubility and dissolution of BNZ. The aim of this work was to enhance its dissolution rate using nanostructured systems as carriers, by formulating BNZ-loaded nanoparticles through the nanoprecipitation method. Acrylic/methacrylic copolymer and BNZ were dissolved in acetone and Pluronic® F68 surfactant was dissolved in distilled water. The organic phase was injected on the aqueous phase at constant flow rate and the resulting suspension was stirred at room temperature to allow the complete evaporation of acetone. Then, thissuspension was filtered and the supernatant was freeze-dried. The characterization of the nanoparticles was carried out by Scanning Electron Microscopy, Differential Scanning Calorimetry and Dynamic Light Scattering. The encapsulation efficiency (%EE) and loading capacity (%LC) were determined by UV-visible spectrophotometry. Polymer/drug interactions were analysed by attenuated total reflectance/Fourier transform-infrared spectroscopy (ATR/FT-IR). The in vitro release of BNZ from the nanoparticles was assessed by the dialysis bag method using. The dissolution profiles were compared using the dissolution efficiency at 20 min (DE20) and 120 min (DE120). Results showed that the yield (%) after freezedrying process was ~85%. The %EE and %LC of the nanoparticles was 96% and 18% w/w, respectively. SEM and DLS analysis showed spherical particles with submicrometer size before and after freeze-drying, low polydispersity index and positive zeta potential. FT-IR spectra of nanoparticles showed characteristic bands of BNZ suggesting that part of drug remained on their surface while thermal analysis revealed that the drug crystallinity after process decreased. In vitro release studies showed an increase of more thantwice in the dissolution rate of drug from nanoparticles. It could be due to the reduction of size and reduced crystallinity of the drug and to that part of BNZ remained on the surface of particles. This study demonstrates that nanoprecipitation is an effective method to enhance the dissolution rate of BNZ and could be used in treatment optimization.