Embryotoxicity of silica nanoparticles in the drug delivery of domperidone in zebrafish.

Domperidone is a dopamine D2 receptor inhibitor that stimulates pituitary gonadotropins. It is usually associated with synthetic GnRHa to promote spawning in fish. However, the route of administration used, intramuscular injection, can be quite stressful. Little is known about the effects of domperidone, as well as other routes. This study aims to evaluate the toxicity of domperidone encapsulated by silica nanoparticles in zebrafish embryos. The study involved four groups with three concentrations: 1. domperidone (DP) 0.0001, 0.0002 and 0.0004 mg/mL; 2. DP associated with silica nanoparticles (SiNPs) 0.0001 + 1.1, 0.0002 + 2.2 and 0.0004 + 4.4 mg/mL; 3. SiNPs 1.1, 2.2 and 4.4 mg/mL and 4. Control (E3), with four repetitions per group. Survival, teratogen and heart rate (HR) were evaluated over a period of 168 hpf. Survival was higher in DP + SiNPs treatment, HR was lower in treatment with 4.4 mg/mL of SiNPs, while treatment with 0.004 mg/mL of DP increased HR. This study demonstrated that the association of DP and SiNPs decreased the toxicity of both DP and SiNPs, demonstrating that this may be a viable alternative to reduce the possible cardiotoxic effects of DP.

Depression, anxiety-like behavior, and memory impairment in mice exposed to chitosan-coated zein nanoparticles.

The advent of biotechnology provided the synthesis of nanoproducts with diverse applications in the field of medicine, agriculture, food, among others. However, the toxicity of many nanoparticles (NP) currently used, which can penetrate natural systems and impact organisms, is not known. Thus, in this study, we evaluated whether the short exposure (5 days) to low concentrations of chitosan-coated zein nanoparticles (ZNP-CS) (0.2 ng/kg, 40 ng/kg, and 400.00 ng/kg) was capable of causing behavioral alterations compatible with cognitive deficit, as well as anxiety and depression-like behavior in Swiss mice. However, we observed an anxiogenic effect in the animals exposed to the highest ZNP-CS concentration (400.00 ng/kg), without locomotor alterations suggestive of sedation or hyperactivity in the elevated plus maze (EPM) test. We also observed that the ZNP-CS caused depressive-like behavior, indicated by the longer immobile time in the tail suspension test and the animals exposed to ZNP-CS presented deficit in recognition of the new object, not related to locomotor alteration in this test. To the best of our knowledge, this is the first report of the neurotoxicity of ZNP in a mammal animal model, contributing to the biological safety assessment of these nanocomposites.