Nanocápsulas de PLGA e gordura de murumuru contendo β-lapachona: preparação, caracterização e atividade citotóxica

Abstract

The β-lapachone (β-lap) is a natural naphthoquinone, found as a minor constituent in some species of ipe (gender Handroanthus Mattos) with pharmacological properties such as antimicrobial, anticancer and trypanocidal activities. However, their therapeutic application is challenging due to its low aqueous solubility, and high toxicity. In order to improve the bioavailability of this compound and increase its safety, different carrier systems with nanometric sizes have been developed. The nanocapsules (NC's) PLGA with oil core of murumuru fat (NCMM) were the choice for this study to encapsulate and load the β-lap. The extraction and synthesis of β-Lap of ipe sawdust lapachol promoted a yield of 92.3%. Using the nanoprecipitation method, the produced nanocapsules containing β-lap (NCMMβ-lap) showed spherical shape, surface roughness, average size between 2.0 and 132.5 ± 1.3 ± 149, polydispersity <0.2, zeta potential of -0.009 ± 0.2 and 0.15 ± 0.2 and an encapsulation efficiency of 94.3%. The NCMMβ-lap cytotoxicity showed dose- and time-dependent for the cell lines NIH/3T3 and MCF7, being more toxic than free β-lap in the same concentrations, and selective for tumor cell line MCF7. The mechanisms of cell death of free β-lap and NCMMβ-lap were very similar, observing ROS, DNA fragmentation, interlock of cells in check phases, and indication of late apoptosis and necrosis. In short, the encapsulation of β-lap potentiated the anticancer activity and suggested greater certainty in the application of this drug, pointing NCMMβ-lap as a promising alternative to enable the use of β-lap at the clinic.