RESUMEN
Iron oxide nanoparticles (IONPs) possess many utilizable physical and chemical properties and have an acceptable level of biocompatibility. Therefore, they are extensively used in different medical applications. Hence, the challenge is to modify the surfaces of prepared iron oxide nanoformulations with a biocompatible coat to enhance their biosafety. In this study, different formulations of IONPs with different capping agents (citrate [Cit-IONPs], curcumin [Cur-IONPs], and chitosan [CS-IONPs]) were prepared and characterized using various physicochemical techniques. The biodistribution of iron and the histopathology of affected tissues were assessed after Cit-IONPs, Cur-IONPs, CS-IONPs, and commercial ferrous sulfate were orally administered to adult female Wistar rats for 10 consecutive days at a dose of 4 mg/kg of body weight/day. The results were compared with a control group injected orally with saline. The iron content in the kidneys, liver, and spleen was measured by atomic absorption spectroscopy. Histopathological alterations were also examined. The biodistribution results demonstrate that iron accumulated mainly in the liver tissue, whereas the lowest liver accumulation was observed after the administration of Cit-IONPs or CS-IONPs, respectively. In contrast, the administration of CS-IONPs displayed the highest spleen iron accumulation. The ferrous sulfate (FeSO4 )-treated group showed the highest kidney iron accumulation as compared with the other groups. The histopathological examination revealed that signs of toxicity were predominant for groups treated with Cit-IONPs or commercial FeSO4 . However, Cur-IONPs and CS-IONPs showed mild toxicity when administered at the same doses. The results obtained in the present study will provide insights into the expected in vivo effects after administration of each nanoformulation.
Asunto(s)
Quitosano , Ácido Cítrico , Curcumina , Nanopartículas Magnéticas de Óxido de Hierro/química , Animales , Quitosano/química , Quitosano/farmacocinética , Quitosano/farmacología , Ácido Cítrico/química , Ácido Cítrico/farmacocinética , Ácido Cítrico/farmacología , Curcumina/química , Curcumina/farmacocinética , Curcumina/farmacología , Femenino , Especificidad de Órganos , Ratas , Ratas Wistar , Propiedades de SuperficieRESUMEN
AIMS: The Blood-Brain Barrier (BBB) is a filter for most medications and blocks their passage into the brain. More effective drug delivery strategies are urgently needed to transport medications into the brain. This study investigated the biodistribution of thymoquinone (TQ) and the effect on enzymatic and non-enzymatic oxidative stress indicators in different brain regions, either in free form or incorporated into nanocarriers as mesoporous silica nanoparticles (MSNs). Lipid bilayer-coated MSNs. MATERIALS AND METHODS: MSNs and LB-MSNs were synthesized and characterized using a transmission electron microscope and dynamic light scattering to determine the particle size and zeta potential. TQ encapsulation efficiency and TQ's release profile from LB-MSNs were also examined. The impact of loading LB-MSNs with TQ-on-TQ delivery to different brain areas was examined using chromatographic measurement. Furthermore, nitric oxide, malondialdehyde (MDA), reduced glutathione, and catalase were evaluated as oxidant and antioxidant stress biomarkers. KEY FINDINGS: The LB-MSNs formulation successfully transported TQ to several areas of the brain, liver, and kidney, revealing a considerable increase in TQ delivery in the thalamus (81.74%) compared with that in the free TQ group and a considerable reduction in the cortex (-44%). The LB-MSNs formulation had no significant effect on TQ delivery in the cerebellum, striatum, liver, and kidney. SIGNIFICANCE: TQ was redistributed in different brain areas after being encapsulated in LB-MSNs, indicating that LB-MSNs have the potential to be developed as a drug delivery system for selective clinical application of specific brain regions. CONCLUSIONS: LB-MSNs are capable nanoplatforms that can be used to target medications precisely to specific brain regions.
Asunto(s)
Nanopartículas , Dióxido de Silicio , Animales , Antioxidantes , Benzoquinonas , Disponibilidad Biológica , Encéfalo , Catalasa , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Glutatión , Membrana Dobles de Lípidos/química , Malondialdehído , Nanopartículas/química , Óxido Nítrico , Oxidantes , Porosidad , Ratas , Ratas Wistar , Dióxido de Silicio/química , Distribución TisularRESUMEN
Depression is a mental illness with a high prevalence in humans reaching 21% of the worldwide population.The present study aims to evaluate the antidepressant effect of different formulations of Thymoquinone; free Thymoquinone (TQ), Thymoquinone-loaded Chitosan nanoparticles (TQ-TPP-Cs NPs) and Thymoquinone-loaded Chitosan nanoparticles coated with polysorbate 80 (TQ-TPP-Cs NPs-PSb80) that have been prepared to avoid the low bioavailability of TQ. Rats were randomly separated into control rats, depression control induced by reserpine, rat model treated with TQ, rat model treated with TQ-TPP-Cs NPs and rat model treated with TQ-TPP-Cs NPs-PSb80. The results indicate that TQ-TPP-Cs NPs loaded with polysorbate 80 was more efficient in ameliorating the behavioral and neurochemical changes induced by reserpine than TQ and TQ-TPP-Cs NPs. Formulationswere characterized for size, morphology, encapsulation efficiency and in vitro drug release before their use in treatment. Reserpine induced a reduction in motor activity and swimming time and increased immobility time as indicated from the open field test (OFT) and forced swimming test (FST). In addition, a significant decrease in the monoamine neurotransmitters serotonin (5-HT), norepinephrine (NE) and dopamine (DA) was recorded in the cortex, hippocampus and striatum of reserpine-treated rats. The present data suggest that the antidepressant efficacy of TQ could be enhanced by engaging TQ with chitosan nanoparticles as a drug carrier and the formulations were modified by coating with polysorbate 80.