Synthesis and characterization of poly(propylene imine) dendrimers, as nanocarriers of Benznidazole: an in vitro controlled release assay

Abstract

Background: American trypanosomiasis, or Chagas disease, is the result of an infection caused by the Trypanosoma cruzi parasite. The disease is endemic in Latin America, where the main clinical manifestation and cause of death of Chagas patients is cardiomyopathy. The current approved treatment for this disease is based on the use of the nitroheterocyclic compound, Benznidazole. The drug is administered in high doses and for prolonged periods, which causes serious adverse effects, eventually leading to treatment discontinuation. In addition, it has only shown efficacy in the acute phase of the disease. Benznidazole has low solubility, low permeability, low bioavailability and high toxicity in the body. These physicochemical characteristics can be improved by using dendritic structures that serve as nanocarriers. Methods: In this research, poly(propylene imine) PPI dendrimers in generations 4.0 G and 5.0 G were synthesized and characterized. We performed the synthesis by divergent approach. We encapsulated Benznidazole using the equilibrium dialysis method, and we evaluated the loading efficiency and the concentration of the released drug by high-performance liquid chromatography (HPLC). Results: Preliminary results showed a drug loading efficiency on the dendrimer of 78% and an entrapment percentage of 99.6%. The release kinetics showed a controlled and sustained release over time compared to dendrimer-free Benznidazole. Conclusions: The PPI 5.0 G - Benznidazole dendrimer system could be considered as an alternative to be evaluated in vitro and in vivo, as an alternative to conventional treatment of Chagas disease. The next stage of the experimental work consists of standardizing an infection model of H9C2 cardiomyocytes with Colombian strains of Trypanosoma cruzi, in order to evaluate the effect of the encapsulated drug on nanocarriers.