RESUMO
This study was designed to examine fetal and maternal toxicity of curcumin (CURC) loaded lipid-core nanocapsules (LNC) prepared with poly(ϵ-caprolactone) as a polymer, administered during the organogenesis period. Free CURC and CURC loaded-LNC (C-LNC) (2 mg/kg), blank LNC (B-LNC) and saline (CONTROL) were administered per oral route from the 7° to 13° gestational day (GD). Dams were evaluated daily for body weight gain, clinical signs, water and food intake. On 20° GD, dams were euthanized, organs were weighed and blood was collected for biochemical determinations. Fetal biometrics and external morphological anomalies were assessed. Also, were performed histopathological analysis of placenta and measurement of cytokines levels in placental and fetal liver tissues. All groups did not cause changes in dams during the pregnancy. Furthermore, treatments did not cause external morphological changes and delayed fetal development. Still, for histopathological analysis of placental tissue, treatments did not cause alterations in evaluated parameters. For cytokines levels, CURC and C-LNC caused a decrease in placental levels of TNF-α. Therefore, we have demonstrated that C-LNC did not cause toxicological effects (mother and fetus), in the same manner as pattern bioactive compound, proving to be a promising nutraceutical delivery system for maternal supplementation with CURC.
Assuntos
Curcumina/administração & dosagem , Desenvolvimento Fetal/efeitos dos fármacos , Lipídeos/química , Nanocápsulas , Placenta/efeitos dos fármacos , Poliésteres/administração & dosagem , Animais , Peso Corporal/efeitos dos fármacos , Citocinas/metabolismo , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Feminino , Masculino , Troca Materno-Fetal , Placenta/metabolismo , Gravidez , Ratos WistarRESUMO
The unloaded polymeric nanocapsules (NCs) present incredible characteristics as drug carriers. However, the toxicity caused by NCs with different coatings is still a challenge for contemporary toxicology. Allied to this, preclinical studies are performed in males, disregarding possible gender-dependent toxicity. Thus, the aim of present study was to evaluate the influence of different NCs coatings on toxicological and behavioral parameters in female rats. The physicochemical characterization of NCs with different surface coatings: NC1 (Polysorbate 80), NC2 (PEG), NC3 (Eudragit®RS 100) and NC4 (Chitosan) were performed. Female rats were treated with saline, NC1, NC2, NC3 or NC4 daily for 14 days, p.o. After 24 h of last treatment, animals were submitted to behavioral tests. Only after behavioral tests, female rats were euthanized, organs were removed and weighted. After, histopathological, biochemical and oxidative stress analysis were performed. All NCs-coatings did not cause alterations in behavioral tests. For markers of hepatic, renal damage and lipid profile, the different coatings showed a low toxicity. NCs did not alter weight of organs and histopathological analysis. Also, all NCs-coatings did not modify redox balance in organs studied, only NC2 induced a increase of FRAP levels in intestine. This study demonstrated that the different NCs-coatings did not cause behavioral changes and showed a low toxicity in female rats.