Nanoparticles as Alternative Strategies for Drug Delivery to the Alzheimer Brain: Electron Microscopy Ultrastructural Analysis

Abstract

One of the biggest problems and challenges for the development of new drugs and treatment strategies against Alzheimer Disease (AD) is the crossing of target drugs into the blood brain barrier. The use of nanoparticles in drug delivery therapy holds much promise in targeting remote tissues, and as a result many studies have attempted to study the ultrastructural localization of nanoparticles in various tissues. However, there are currently no in vivo studies demonstrating the ultrastructural distribution of nanoparticles in the brain. The aim of this study was to address how intraperitoneal injection of silver nanoparticles in the brain leads to leaking on the inter-endothelial contact and luminal plasma membrane, thus elucidating the possibility of penetrating into the most affected areas in the Alzheimer brain (vascular endothelium, perivascular, neuronal and glial cells). Our results show that the silver nanoparticles reached the brain and were found in hippocampal areas, indicating that they can be conjugated and used to deliver the drugs into the cell cytoplasm of the damaged brain cells. The present study can be useful for the development of novel drug delivering therapy and useful in understanding the delivery, distribution and effects of silver nanoparticles in AD brain tissue at cellular and subcellular level.

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“…Silver nanoparticles (AgNPs) have also been explored for brain-targeted drug delivery. After intraperitoneal injection, the AgNPs reached and accumulated in the hippocampus, which is known to be an essential region for NDs [108]. It was noted that a 5µg/mL dose of these nanoparticles could induce an inflammatory and neurodegenerative gene expression response in mice's neural cells [98,109].…”

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“…Silver nanoparticles have been investigated for their ability to cross the BBB and induce an immune response in the brain. When injected intraperitoneally, the AgNPs can reach the hippocampus, an important region for neurodegenerative disorders [41]. AgNPs naturally have antibacterial characteristics that make them promising in some cases, but they induce inflammatory and neurodegenerative gene expression responses at 5 μg/mL dose in mouse neural cells [42].…”

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“…It can be utilized in imaging through X-rays or micro-CT scanning [18,19]. Silver nanoparticles (AgNPs) can be injected intraperitoneally and then they can reach the hippocampus fast [20]. In addition, silver has antibacterial characteristics, which cause anti-inflammatory effect and reduce reactive oxygen species (ROS).…”