Mariana Morris (Advisor), Saber M. Hussain (Advisor), Ioana Pavel Sizemore (Committee Member)
Master of Science (MS)
Gold nanoparticles (GNPs) possess unique physicochemical properties that may facilitate entry into the central nervous system (CNS) where they may act therapeutically. There is little information on biodistribution or inflammatory effects of GNPs in specific brain regions. Brain Localization and neuroinflammatory response to citrate-capped spherical GNP (10 nm) was determined 24 hours after intravenous (IV) injection in male C57Bl mice. A known inflammogen, lipopolysaccharide (LPS, 2 mg kg-1, SC), was tested as a positive control supplement. Aggregation of GNPs was measured using various Phosphate-Buffered Saline (PBS) concentrations (10, 1, 0.1, 0.01 X) to determine the optimal buffer concentration to maintain GNP solubility. 0.01 X PBS was used in all studies, since it produced the least amount of GNP aggregation. The next experiment verified entry of GNPs into the CNS. Mice were injected IV (200 µg mL-1 10 nm GNP in 0.01 X PBS) via the tail vein. After 24 hours mice were euthanized (with 130 mg ml-1 Euthasol), and perfused transcardially (with 2% glutaraldehyde and 2% paraformaldehyde), then brains were removed. GNP concentrations were measured using inductively coupled plasma mass spectrometry in whole brain homogenates. To specifically localize accumulation of GNPs in brain, septum, caudate, hippocampus, hypothalamus, cortex, frontal cortex, and spinal cord regions were micro dissected. Hypothalamus, hippocampus, and septum had the highest GNP levels (6.7, 6.2, and 4.6 µg Au g-1 tissue respectively). To evaluate brain inflammation, we used q-PCR analysis of frozen brain regions for study of pro-inflammatory mediators, Leukemia inhibitory factor (LIF), CC chemokine ligand 2 (CCL2) and Interleukine-1 ß (IL-1ß). GNPs did not affect cytokine/chemokine expression in cortex, frontal cortex or hippocampus. LPS (positive control), as expected, caused a marked (100-fold) increase in the same cytokines. Results show that GNPs enter brain and concentrate in specific regions without eliciting an inflammatory response. Data raise the possibility of usefulness of GNPs in drug delivery and therapeutic treatment of CNS diseases.22
Department or Program
Department of Pharmacology and Toxicology
Year Degree Awarded
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