Clinical Pharmacology & Biopharmaceutics
Open Access

Abstract

One of the biggest problems and challenges in the development of new drugs and/or treatment strategies for Alzheimer disease (AD) is the difficulty of passing the drugs across the blood brain barrier (BBB). 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 even in normal physiological conditions. The object of this study is to illuminate how injection of silver nanoparticles in the brain lead to leaking on the interendothelial contact and endothelial luminal plasma membrane, elucidating the possibility of penetrating into the areas of the brain which are most affected by AD (hippocampal tissues cellular compartment: vascular endothelium, perivascular, neuronal and glial cells). We investigated the ultrastructural distribution of nanoparticles [silver ion (5 nm), final concentration 0.9% which is dissolved in 0.9% NaCl,) in the rat brain hippocampal tissue one and four days after intra-peritoneal (i.p.) injection. The control experiment animals were given the same amount of vehicle treatment (0.9% NaCl, total amount 1 ml) for one and four days. At the end of the experiment perfusion fixation brain tissue was collected for electron microscopic analysis. Randomly selected ultrathin sections of the CA1 and CA3 areas with and without count staining were examined using a transmission electron microscope operating system at 100kV. Images were randomly selected and captured using a Digital Image system. Control animals which received vehicle injection revealed typical ultrastructural morphology of brain microvessels and neurons. The animals that received nanoparticles injection showed that after one and four days of silver injection, varying sizes of silver aggregates were seen throughout the neuronal cell bodies. Very often neuronal cell bodies were characterized by the absence of organelles, including mitochondria which coexisted with the presence of silver particles. The accumulation of the silver particles was also associated with the extracellular matrix, which was observed to coexist in the presence of a flake-like structure surrounding the neuronal tissue after four days of silver injection, and appeared to be a permanent feature of the hippocampal tissue. An interesting characteristic of the brain tissue appeared to be the disruption of the interendothelial contacts in an area where silver ions were present, which indicated that using nanoparticles in in vivo conditions is clearly undesirable in treatment, and that expanding this study in the future to include multiple dosages for comparison is necessary. Therefore this study can be basis for future conjugated silver nanoparticles drugs which able to deliver into the cell cytoplasm, therefore being able to diminish the lesions that occur in AD brain.

Biography

Email: aliev03@gmail.com