In vitro schistosomicidal activity of the lignan (−)-6,6′-dinitrohinokinin (DNHK) loaded into poly(lactic-co-glycolic acid) nanoparticles against Schistosoma mansoni

Abstract

Context: (−)-6,6′-Dinitrohinokinin (DNHK) display remarkable antiparasitic activity and was, therefore, incorporated into a nanoparticle formulation.

Objective: Incorporation of DNHK in poly lactic-co-glycolic acid (PLGA) nanoparticles aiming to improve its biological activities.

Materials and methods: Synthesis, characterization and incorporation of DNHK into glycolic acid (PLGA) nanoparticles by nanoprecipitation method. The nanoparticles were characterized by ultraviolet-visible spectroscopy, X-ray diffraction, field emission electron microscopic scanning mansoni (FESEM), and dynamic light scattering (DLS). For the in vitro test with Schistosoma mansoni, the DNHK-loaded PLGA was diluted into the medium, and added at concentrations 10–200 µM to the culture medium containing one adult worm pair. The parasites were kept for 120 h and monitored every 24 h to evaluate their general condition, including: pairing, alterations in motor activity and mortality.

Results: The loaded PLGA nanoparticles gave an encapsulation efficiency of 42.2% and showed spherical characteristics in monodisperse polymeric matrix. The adult worm pairs were separated after 120 h of incubation for concentrations higher than 50 µM of DNHK-loaded PLGA. The groups incubated with 150 and 200 µM of DNHK-loaded PLGA for 24 and 120 h killed 100% of adult worms, afforded LC₅₀ values of 137.0 ± 2.12 µM and 79.01 ± 1.90 µM, respectively, which was similar to the effect displayed by 10 µM of praziquantel.

Discussion and conclusions: The incorporation of DNHK-loaded showed schistosomicidal activity and allowed its sustained release. The loaded PLGA system can be administered intravenously, as well as it may be internalized by endocytosis by the target organisms.

Keywords:

• PLGA
• biological activity
• nanoparticulate formulation
• 6,6′-dinitrohinokinin
• schistosomicidal

Acknowledgements

The authors also thank the Surface and Colloid Laboratory of the School of Philosophy, Sciences and Languages of Ribeirão Preto-University of São Paulo.

Disclosure statement

The authors declare that there is no conflict interest.

Additional information

Funding

The authors are thankful to the Brazilian Funding Agencies: São Paulo Research Foundation (FAPESP), grants # 2011/05952-4, 2010/17378-8 and 2009/05049-2; CNPq for fellowships (Numbers 303349/2013-1, 401630/2014-5 and 553287/2009-5) related to this work.