Biopharmaceutical evaluation of benznidazole-loaded microparticles: In vitro and in vivo studies

Benznidazole, one of only two approved treatments for Chagas disease, exhibits poor water solubility (<0.04 mg/mL), limiting its oral absorption and bioavailability. This study aimed to develop benznidazole-loaded microparticles with enhanced dissolution and improved oral bioavailability. Microparticles were prepared by spray-drying using Eudragit® RS PO, Eudragit® RL PO, or a 1:1 blend of both polymers. Physicochemical characterization included particle size, zeta potential, surface morphology, drug loading, encapsulation efficiency, yield, stability, crystallinity, mucoadhesive properties, and in vitro dissolution. Oral pharmacokinetics were evaluated in Wistar rats. The resulting microparticles were spherical, with sizes ranging from 5.02 to 7.17 µm and a positive zeta potential (7.27-11.77 mV). The yield was approximately 63 %, with drug loading ranging from 12.37 % to 14.68 % and an encapsulation efficiency between 66.50 and 78.91 %. X-ray diffraction revealed a reduced crystallinity of the encapsulated drug. Both drug loading and the partial amorphization of the encapsulated drug were maintained during long-term storage. The mucoadhesion assay confirmed the presence of significant interactions between the microparticles and mucin. In vitro dissolution studies confirmed that the microencapsulation process improved the dissolution rate of benznidazole, whereas in vivo evaluations in rats showed a five-fold enhancement in oral bioavailability relative to the raw benznidazole formulation, highlighting the efficiency of the developed delivery system. Overall, these findings underscore the potential of benznidazole-loaded microparticles as a promising approach to enhance oral therapy for Chagas disease.