Caracterização biológica de nanopartículas de contendo curcumina

Abstract

The application of nanotechnology in medicine is a promising strategy. The use of safe, biocompatible and biodegradable nanocarriers aims at modifying the biodistribution and transmembrane passage of drugs in order to improve their efficacy performance and reduce their side effects by selectively transporting active molecules to target tissues. Blood-brain barrier is a complex and highly regulatory system whose restrictive effect ultimately limits the therapy of several neuropathologies, including Alzheimer's disease (AD). Another important membrane whose study of nanoencapsulated drugs and their effects on the fetus has been poorly studied is the placental membrane. The use of drugs during pregnancy is risky, however, the treatment of diseases that affect the mother or fetus is fundamental. Curcumin (CURC) is a polyphenol extracted from Curcuma longa L. rhizome, whose protective and therapeutic properties are widespread but have low stability and bioavailability. Thus, nanotechnology may be an alternative to carry curcumin by modifying its passage through biological membranes. In this context, this work evaluated the effects of CURC-containing lipid core nanocapsules (LNC) in an animal model of AD and in an animal model of gestation. First, Swiss mice were used, which received Aβ1-42 intracerebroventricular injection. Animals were treated orally for 14 days with Saline, CURC (50 mg/kg), LNC (10 mg/kg) and LNC (1 mg/kg). On the 14th and 15th day the animals were submitted to behavioral test and later to euthanasia. LNC showed significant neuroprotection against Aβ1- 42-induced behavioral and neurochemical changes even at doses 10 and 50 times lower than free curcumin. These data suggest that curcumin nanoencapsulation may be a promising preventive and therapeutic alternative for AD. Subsequently, LNC prenatal toxicity was evaluated. Pregnant females were euthanized at GD 20, followed by maternal and fetal examination. The results showed that there was no difference in the weight evolution of the dams, as well as in hematological and hormonal parameters, indicating the absence of maternal toxicity. No external anomalies or delayed fetal development were observed. CURC and LNC reduced placental TNF-α levels. Similarly, no histopathological changes were observed in the placenta. Further studies are needed to evaluate nanoparticle biodistribution during pregnancy. This study showed that lipid-core nanocapsules did not cause maternal or fetal toxic effects, which will facilitate the development of future therapies to treat and manage complicated pregnancies.