Evaluation of lignan-loaded poly(ε-caprolactone) nanoparticles: synthesis, characterization, in vivo and in silico schistosomicidal activity

Abstract

Lignan dinitrohinokinin displays important biological activities, which led to the preparation of its poly-ε-caprolactone nanoparticles. Kinetics analysis revealed initially slow drug release followed by a prolonged, moderate release 6 h later due to DNHK diffusion through the polymeric matrix. Molecular dynamics simulations show that DNHK molecules that interact stronger with other DNHK molecules near the PCL/DNHK surface are more difficult to dissociate from the nanoparticle. The smaller diameter nanocapsules with negative surface charge conferred good colloidal stability. The formulations showed a size distribution with monodisperse systems formation. In vivo evaluation of schistosomicidal activity against Schistosoma mansoni showed that DNHK, when incorporated into nanoparticles, caused egg number reduction of 4.2% and 28.1% at 40 mg/kg and 94.2% and 84.4% at 400 mg/kg in the liver and the spleen, respectively. The PCL nanoparticles were stable in aqueous dispersion and could be optimized to be used as a promising lignan release agent.

Graphical Abstract

Keywords:

• (−)-6,6’-dinitrohinokinin (DNHK)
• polymeric nanoparticles
• schistosomicidal activity
• anti-inflammatory activity

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This study was funded by (FAPESP, grants # 2011/07623-8, 2011/05952-4, 2010/17378-8, 2009/15207-4 and 18/25010-2), (CAPES n°001) and (CNPq) fellowships # 313648/2018-2, 303349/2013-1, 401630/2014-5, 306271/2017-6 and 553287/2009-5.