Atividade esquistossomicida de substâncias naturais em nanopartículas lipídicas sólidas

Abstract

Schistosomiasis, caused by Schistosoma mansoni, remains a serious public health problem in the world and Brazil, being present in the list of Neglected Tropical Diseases (NTDs) of the World Health Organization (WHO). In Brazil, Minas Gerais (MG) is the state most affected by the disease. Currently, there are a large number of patients and the treatment is only done with a drug (praziquantel), ineffective against young forms of parasites and to reports of resistance. Therefore, research for new schistosomiasis drugs becomes very important. The use of natural substances stands out in this scenario and cardamonin and licochalcone A are chalcones with schistosomicidal activities already registered in the literature. Nanotechnology allows the incorporation of active substances into nano-scale systems which, in turn, decrease toxicity and increase the bioavailability of drugs. Solid lipid nanoparticles (SLN) are an interesting nano system because they are composed of mostly biocompatible lipids. The association of nanotechnology and natural products was used in this work for a possible treatment of schistosomiasis. SLN were developed by high shear homogenization and characterized for its zeta potential, particle size, polydispersion index (PdI), encapsulation efficiency, in vitro release, stability and cytotoxicity. Toxicity assays shows that nanoparticles decrease the toxicity of the substances in front of macrophages J774 cell line and hemolysis. The formulations were tested in vitro and in vivo against adult S. mansoni worms and decresed the viability of parasite. In vitro, cardamonin incorporated in SLN caused the death of 100% of the parasites in 24 hours at the concentration of 25 μM, in addition to significant reduction in the motor activity of the parasites. These results were similar to that of free cardamonin. SLN with licochalcone A caused the death of adult worms in a concentration lower than the free licochalcone A. In vivo, when orally administered, the nanoparticle with licochalcone A decreases 30% of the parasites, while the free substance was ineffective. By the peritoneal administration, free and encapsulated licochalcone A reduced more than 50% of the parasites. The results indicate that SLN containing encapsulated actives are a safe alternative for the host in the treatment of schistosomiasis.