Multi-kinetic release of benznidazole-loaded multiparticulate drug delivery systems based on polymethacrylate interpolyelectrolyte complexes

NICOLAS PONCE; RUBEN MANZO; MARISA MARTINELLI; MARIA PILAR AOKI; MONICA GARCIA; LILIANA SANMARCO; ALVARO JIMENEZ KAIRUZ; NICOLAS PONCE; MARISA MARTINELLI; RUBEN MANZO; MARIA PILAR AOKI; MONICA GARCIA; LILIANA SANMARCO; ALVARO JIMENEZ KAIRUZ

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2018 vol. 120 p. 107 - 122

0928-0987

Interpolyelectrolyte complexes (IPEC) formulated as multiparticulate drug delivery systems (MDDS) are interestingcarriers to improve drug? performance. Benznidazole (BZ) is the first?line drug for Chagas treatment;however, it presents side effects and toxicity, conditioning its efficacy and safety. The goal of this work was toobtain novel MDDS composed by IPEC based on different polymethacrylate carriers loaded with BZ and toinvestigate in vitro drug delivery performance for oral administration. Physicochemical characterizations werestudied and preclinical studies in a murine model of acute Chagas disease were also performed. The MDDScomposed by BZ-loaded IPEC based on polymethacrylates were obtained by casting solvent followed by wetgranulation methods with yields > 83%. FT-IR demonstrated ionic interaction between the polyelectrolytes.Confocal microscopy, DSC and PXRD revealed a fraction uniformly distributed of free BZ on the multiparticles.The rheological evaluation of the MDDS showed adequate flow features for their formulation in hard gelatincapsules.The type and composition of IPEC conditioned the modulation of BZ release and fluid uptake results.MDDS based on more hydrophylic Eudragit® showed very fast dissolution (Q15min > 85%), while an extendedrelease (Q120min ≤ 40%) for the hydrophobic ones was observed. Capsules containing a combination of twoMDDS with different release profile of BZ showed promising properties to improve Chagas disease pharmacotherapyin the preliminary in vivo assay performed, in which the BZ-loaded MDDS exhibited efficacy to reduceparasitemia, while decreasing the levels of liver injury markers in comparison to BZ conventional treatment.Multi-kinetic BZ delivery systems developed are interesting pharmaceutical alternatives to improve the treatmentof Chagas disease.