Nanoparticle uptake into the brain following intranasal instillation in mice
CeO2 nanoparticles (NPs) are nanomaterials defined as poorly soluble particles with low toxicity (PSPL). CeO2 NPs are commonly used as polishing agent, as fuel additive to promote combustion and as sub catalyst for automotive exhaust cleaning. NM-300K are known silver nanoparticles (AgNPs) previously used in the European Project NanoReg and demonstrated to have toxic properties in vitro. Use of AgNPs in consumer goods has become increasingly prevalent due to their antimicrobial properties. Textiles, aerosol sprays, water purification systems, and coatings on medical implants and instruments may contain AgNPs. These variegate applications of CeO2 and AgNPs may increase risk of exposure to humans and the environment. Exposure to nanoparticles may results in their translocation into the brain from the nasal cavity via a direct uptake from olfactory bulb or trigeminals nerve or indirectly through the cerebral spinal fluid or across the blood-brain barrier. Accumulating evidence have shown that aerosol exposure of nanoparticles, can be linked to the increase of neurodegenerative diseases such as Alzheimer. One of the aims of this study will be to establish and develop at STAMI an intranasal instillation exposure method. The intranasal exposure is an advantageous method that has been proved to minimize systemic exposure and thus potential systemic side effects. It is non-invasive, easy to perform and has more toxicological relevance than intra-tracheal administration.
In this study, we are going to expose wild type mice (C57BL/6J) with CeO2 NPs and AgNPs through intranasal instillation. Since size and distribution play a role in differing effects on biological systems, it will be of interest to determine whether variability in size and composition might influence the location of nanoparticles in the CNS and resultant effect.
Based on literature research, successfully intranasal instillation experiments in mice where CeO2 NPs and AgNPs were used, the applied dosage was respectively of 40 mg/kg and 50mg/Kg. We will use those as reference in our study.
The main aim of this study is to examine the presence and distribution of CeO2 NPs and AgNPs in the brain following intranasal instillation and to assess using histochemical techniques whether any alterations in brain ultrastructure occur. Animal studies are necessary for our purpose as there are no suitable in vitro cell culture models available to study nanoparticle translocation in complex biological systems. In this study, we will use 85 female wild type mice.
In this study, we are going to expose wild type mice (C57BL/6J) with CeO2 NPs and AgNPs through intranasal instillation. Since size and distribution play a role in differing effects on biological systems, it will be of interest to determine whether variability in size and composition might influence the location of nanoparticles in the CNS and resultant effect.
Based on literature research, successfully intranasal instillation experiments in mice where CeO2 NPs and AgNPs were used, the applied dosage was respectively of 40 mg/kg and 50mg/Kg. We will use those as reference in our study.
The main aim of this study is to examine the presence and distribution of CeO2 NPs and AgNPs in the brain following intranasal instillation and to assess using histochemical techniques whether any alterations in brain ultrastructure occur. Animal studies are necessary for our purpose as there are no suitable in vitro cell culture models available to study nanoparticle translocation in complex biological systems. In this study, we will use 85 female wild type mice.