Characterization and Trypanocidal Activity of Nifurtimox-containing and Empty Nanoparticles of Polyethylc y anoacrylates

Abstract

The aim of this study was to evaluate the utility of nanoparticles of polyalkylcyanoacrylate as a targeted delivery system for nifurtimox against Trypanosoma cruzi, responsible for Chagas' disease. Ethylcyanoacrylate nanoparticles were prepared by an emulsion polymerization process and formulations containing different concentrations of nifurtimox, polyethylcyanoacrylates and surfactants were investigated and analysed for size and drug content. The nanoparticles obtained were less than 200 nm in size, as measured by electron microscopy and cytometry. The peak percentage of nifurtimox uptake into the nanoparticles was 33.4% for use of 500 microL polyethylcyanoacrylate, 200 microL surfactant (Tween 20) and 10 mg nifurtimox in 50 mL polymerization medium. The highest release of nifurtimox from the nanoparticles was 65.4% after 6-h incubation at pH 7.4. In-vitro studies using cultures of T. cruzi epimastigotes revealed considerably increased trypanocidal activity compared with a standard solution of nifurtimox. Studies of cell cultures previously infected with metacyclic forms of the parasite showed that only 2-h treatment with solutions of 0.001% of the nanoparticle suspension reduced parasitism by 87-94% both when the nanoparticles were loaded with nifurtimox and when unloaded. Electron-microscopic examination revealed processes of degeneration and lysis, suggesting apoptotic processes, in intracellular amastigotes and free amastigotes treated with the nanoparticles. It was demonstrated that unloaded nanoparticles, by mechanisms not completely elucidated, have trypanocide activity similar to that of a standard solution of nifurtimox. It is concluded that the nanoparticles loaded with nifurtimox constitutes a good carrier of the drug against T. cruzi. The loaded-nanoparticles significantly increase trypanocidal activity.

Novel gel-like microemulsion for topical delivery of Amphotericin B

“…However, blank formulation had inhibitory activity of parasite growth, 75.04 ± 11.20% with no difference respect to AmB-loaded gel-like ME (p > 0.05); this fact was also reported for AmB solubilized with poloxamer 188 in a micellar formulation [42]. Furthermore, surfactants had strong lytic effect against Trypanosoma cruzi, a parasite of the same family as Leishmania, as was the case of Tween 20 and polyethylcyanoacrylate nanoparticles which had activity against parasite cells and enhanced activity of nifurtimox [43][44][45]. Surfactants modify parasite membrane, producing change in fluidity and leakage of vital substances, although in our study there was not synergism [46].…”

A Critical Review on Chagas Disease Chemotherapy

“…Also in studies with T. cruzi, it was already been shown to increase in vitro and in vivo effect of different drugs. For example the use of ethylcyanoacrylate nanoparticles prepared by an emulsion polymerization process together with allopurinol or Nif and surfactants led to higher activity against epimastigotes than the corresponding free compound (Gonzalez-Martin et al 1998. Also Molina et al (2001) incorporated inhibitors of sterol biosynthesis into long-circulating polyethyleneglycol-polylactide nanospheres improving the bioavailability of these poorly soluble compounds and increasing the cure rate in experimental animals.…”

Sesquiterpene Lactone in Nanostructured Parenteral Dosage Form Is Efficacious in Experimental Chagas Disease

“…This method is notably simple and provides homogeneous dispersion of colloidal particles containing lipophilic drugs suitable for parenteral administration (37). Compared to the parasitic disease leishmaniasis, only a small number of studies have reported the treatment of T. cruzi experimental infection using nanocarriers (38)(39)(40)(41).…”