Chitosan-based nanodelivery systems applied to the development of novel triclabendazole formulations

LEONARDI, DARÍO; REAL, DANIEL; SALOMON, CLAUDIO; HOFFMANN, STEFAN; GOYCOOLEA, FRANCISCO M.

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2018 vol. 13 p. 1 - 17

1932-6203

Triclabendazole is a poorly-water soluble (0.24 μg/mL) compound classified into the Class II/IVof the Biopharmaceutical Classification System. It is the drug of choice to treat fascioliasis, aneglected parasitic disease worldwide disseminated. Triclabendazole is registered as veterinarymedicine and it is only available for human treatment as 250 mg tablets. Thus, the aim ofthis work was to develop novel drug delivery systems based on nanotechnology approaches.The chitosan-based nanocapsules and nanoemulsions of triclabendazole were fully characterizedregarding their particle size distribution, polydispersity index and zeta potential, in-vitrorelease and stability in biological media. Cytotoxicity evaluation and cellular uptake studiesusing CaCo-2 cell line were also investigated. The results indicated an average hydrodynamicsize around ~160 nm were found for unloaded nanoemulsions which were slightly increasedup to ~190 nm for loaded one. In contrast, the average hydrodynamic size of the nanocapsulesincreased from ~160 nm up to ~400 nm when loaded with triclabendazole. The stability studiesupon 30 days storage at 4, 25 and 37˚C showed that average size of nanoemulsions was notmodified with varying amounts of loaded TCBZ while an opposite result was seen in case ofloaded nanocapsules. In addition, a slight reduction of zeta potential values over time wasobserved in both triclabendazole nanosystems. Release of TCBZ from nanoformulations over6 h in simulated gastric fluid was 9 to 16-fold higher than with untreated TCBZ dispersion. Inphosphate buffer saline solution there was no drug release for neither nanocapsules nornanoemulsions. Cell viabilities studies indicated that at certain concentrations, drug encapsulationcan lower its cytotoxic effects when compared to untreated drug. Confocal laser scanningmicroscopy study has shown that nanocapsules strongly interacted with Caco-2 cells in vitrowhich could increase the passage time of triclabendazole after oral administration. The resultsof this study constitute the first step towards the development of nanoformulations intended forthe oral delivery of anti-parasitic drugs of enhanced bioavailability.