Desenvolvimento de uma formulação de carreador lipídico nanoestruturado contendo partenolido com ação esquistossomicida

Abstract

Schistosomiasis remains one of the most impactful neglected tropical diseases worldwide, characterized by high morbidity and limited therapeutic diversity, with praziquantel being the only drug widely used in control programs. Parthenolide, a sesquiterpene lactone isolated from Tanacetum parthenium, exhibits relevant antischistosomal activity in vitro; however, its therapeutic application in vivo is severely restricted by unfavorable biopharmaceutical properties, including low aqueous solubility, chemical instability, and poor oral bioavailability. In this context, the present study aimed to develop, characterize, and evaluate nanostructured lipid carriers (NLC) containing parthenolide as a pharmaceutical strategy to enhance its therapeutic efficacy against schistosomiasis mansoni. Parthenolide was initially isolated by chromatographic fractionation of the plant extract, achieving purity higher than 96%, as confirmed by high-performance liquid chromatography coupled with diode array detection and nuclear magnetic resonance spectroscopy. Nanostructured lipid carriers were subsequently developed using a hybrid lipid matrix and exhibited mean particle size below 200 nm, polydispersity index lower than 0.3, zeta potential above |30| mV, and encapsulation efficiency exceeding 77%. The in vitro release profile of parthenolide from NLC (1.64% ± 0.012% e 14.13 ± 1.17%) demonstrated controlled release behavior across different dissolution media (pH 1.2 and 6.8), in contrast to the rapid release observed for the free compound (2.25% ± 0.016% and 64.46 ± 0.14%). In assays with adult Schistosoma mansoni worms, the nanoencapsulated formulation showed a significant reduction in EC₅₀ values and a marked increase in selectivity index compared with free parthenolide. In the in vivo experiments using a murine model of schistosomiasis, NLC-parthenolide promoted approximately 78% reduction in total worm burden and more than 70% decrease in fecal egg excretion, whereas non-encapsulated parthenolide did not produce statistically significant therapeutic effects. A reduction in the proportion of immature eggs was also observed, indicating a direct impact on parasite reproductive capacity. These findings demonstrate that nanoencapsulation was essential to overcome the pharmacokinetic limitations of parthenolide, providing controlled drug release, improved bioavailability, and substantially enhanced therapeutic efficacy. Therefore, nanostructured lipid carriers containing parthenolide represent a promising platform for the development of new therapeutic approaches for schistosomiasis and contribute to expanding the pharmacological arsenal against neglected parasitic diseases.