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

Author(s):Show less -

Lima, Thais C. ; Lucarini, Rodrigo ; Luz, Priscilla P. ; de Faria, Emerson H. ; Marcal, Liziane ; Magalhaes, Lizandra G. ; Badoco, Fernanda R. ; Esperandim, Viviane R. ; Molina, Eduardo F. ; Laurentz, Rosangela S. ; Lima, Regiane G. ; Cunha, Wilson R. ; Bastos, Jairo K. ; Andrade Silva, Marcio L.

• Document type: Journal article
• Source: Pharmaceutical Biology; v. 55, n. 1, p. 7-pg., 2017-12-01.

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 mu M to the culture medium containing one adult worm pair. The parasites were kept for 120h and monitored every 24h 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 120h of incubation for concentrations higher than 50 mu M of DNHK-loaded PLGA. The groups incubated with 150 and 200 mu M of DNHK-loaded PLGA for 24 and 120h killed 100% of adult worms, afforded LC50 values of 137.0 +/- 2.12 mu M and 79.01 +/- 1.90 mu M, respectively, which was similar to the effect displayed by 10 mu M 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. (AU)

• FAPESP's process: 09/05049-2 - Development of polymeric nanaparticles and biodegradable systems containing lignans and evaluation its Chagas disease and schistosomiasis activities in vitro and in vivo
• Grantee: Márcio Luís Andrade e Silva
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/05952-4 - Preparation and characterization of polymeric nanoparticles containing (-)-6,6'-dinitrohinokinin and (±)-licarina-A as potential drugs in the assessment of the schistosomicidal activity
• Grantee: Thaís Coelho Lima
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/17378-8 - Study of the immunomodulatory activity of lignans and neolignans obtained by partial synthesis and oxidative coupling as a potential in developing new antiparasitic drugs
• Grantee: Márcio Luís Andrade e Silva
• Support Opportunities: Regular Research Grants