Matching Items (4)
Filtering by
- All Subjects: Nanoparticles
- Creators: Kodibagkar, Vikram
- Creators: Ceton, Ricki Ronea
- Member of: Barrett, The Honors College Thesis/Creative Project Collection
Description
The main objective of this research is to develop and characterize a targeted contrast agent that will recognize acute neural injury pathology (i.e. fibrin) after traumatic brain injury (TBI). Single chain fragment variable antibodies (scFv) that bind specifically to fibrin have been produced and purified. DSPE-PEG micelles have been produced and the scFv has been conjugated to the surface of the micelles; this nanoparticle system will be used to overcome limitations in diagnosing TBI. The binding and imaging properties will be analyzed in the future to determine functionality of the nanoparticle system in vivo.
ContributorsRumbo, Kailey Michelle (Author) / Stabenfeldt, Sarah (Thesis director) / Kodibagkar, Vikram (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
Smart contrast agents allow for noninvasive study of specific events or tissue conditions inside of a patient's body using Magnetic Resonance Imaging (MRI). This research aims to develop and characterize novel smart contrast agents for MRI that respond to temperature changes in tissue microenvironments. Transmission Electron Microscopy, Nuclear Magnetic Resonance, and cell culture growth assays were used to characterize the physical, magnetic, and cytotoxic properties of candidate nanoprobes. The nanoprobes displayed thermosensitve MR properties with decreasing relaxivity with temperature. Future work will be focused on generating and characterizing photo-active analogues of the nanoprobes that could be used for both treatment of tissues and assessment of therapy.
ContributorsHussain, Khateeb Hyder (Author) / Kodibagkar, Vikram (Thesis director) / Stabenfeldt, Sarah (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor)
Created2014-05
Description
Neurological disorders are difficult to treat with current drug delivery methods due to their inefficiency and the lack of knowledge of the mechanisms behind drug delivery across the blood brain barrier (BBB). Nanoparticles (NPs) are a promising drug delivery method due to their biocompatibility and ability to be modified by cell penetrating peptides, such as transactivating transciptor (TAT) peptide, which has been shown to increase efficiency of delivery. There are multiple proposed mechanisms of TAT-mediated delivery that also have size restrictions on the molecules that can undergo each BBB crossing mechanism. The effect of nanoparticle size on TAT-mediated delivery in vivo is an important aspect to research in order to better understand the delivery mechanisms and to create more efficient NPs. NPs called FluoSpheres are used because they come in defined diameters unlike polymeric NPs that have a broad distribution of diameters. Both modified and unmodified 100nm and 200nm NPs were able to bypass the BBB and were seen in the brain, spinal cord, liver, and spleen using confocal microscopy and a biodistribution study. Statistically significant differences in delivery rate of the different sized NPs or between TAT-modified and unmodified NPs were not found. Therefore in future work a larger range of diameter size will be evaluated. Also the unmodified NPs will be conjugated with scrambled peptide to ensure that both unmodified and TAT-modified NPs are prepared in identical fashion to better understand the role of size on TAT targeting. Although all the NPs were able to bypass the BBB, future work will hopefully provide a better representation of how NP size effects the rate of TAT-mediated delivery to the CNS.
ContributorsCeton, Ricki Ronea (Author) / Stabenfeldt, Sarah (Thesis director) / Sirianni, Rachael (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
There is growing interest in intranasal delivery of therapeutics because of direct nose-to-brain pathways which are able to bypass biological barriers, such as the blood-brain barrier (BBB), that have historically limited our ability to effectively deliver drugs to the central nervous system (CNS). Since these pathways were first discovered, there has been significant preclinical success in delivering a wide range of therapeutics to the CNS with additional growing efforts to further improve delivery through nanoparticle drug delivery systems. Here we sought to improve intranasal delivery of DiR, a lipophilic small molecule cyanine dye, to the CNS by surface modifying a poly (lactic-co-glycolic acid) (PLGA) nanoparticle with a short peptide derived from the rabies virus glycoprotein (RVG). The specific aims of this thesis were to evaluate administration route-dependent delivery of RVG nanoparticles to the CNS, and to identify anatomical transport pathways by which nanoparticles facilitate transport of small lipophilic molecules. Route-dependent delivery kinetics and distribution were studied by administering DiR loaded nanoparticles to healthy Balb/C mice. Specific tissues were homogenized and the fluorescent intensity of DiR was measured and compared to control tissue spiked with known amounts of dye. While bioavailability of DiR after intranasal administration was near 0% with minimal exposure to peripheral organs, quick and efficient delivery to the CNS was still observed. CNS delivery after intranasal administration was rapid with peak concentrations at 30 minutes post-administration followed by broad clearance by 2 hours. Regional differences of delivery of DiR to the CNS demonstrated engagement of direct nose-to-brain transport pathways with high delivery being observed to the olfactory bulb, brain stem, and trigeminal nerve. RVG modification however presented only modest targeting benefits. In conclusion, the biodistribution of DiR after intranasal administration of DiR loaded nanoparticles showed high potential for the direct nose-to-brain delivery while limiting peripheral exposure of lipophilic small molecule drugs.
ContributorsChung, Eugene Paul (Author) / Kodibagkar, Vikram (Thesis director) / Sirianni, Rachael (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05