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Title: Polymeric Nanoparticles for Use as Gadolinium-Based Magnetic Resonance Imaging Contrast Agents
Authors: Lee, Yeri
Advisors: Prud'homme, Robert K.
Department: Chemical and Biological Engineering
Class Year: 2015
Abstract: Medical imaging is an important tool in modern medicine for the purpose of diagnosis, therapy, and research. Magnetic resonance imaging (MRI) is a powerful clinical imaging tool as it is noninvasive and provides a higher level of detail compared to other imaging methods, making it an important tool for early diagnosis. Early detection of small lesions is especially important when cancers metastasize as the number, size, and location of lesions affect the treatment regime and patient outcome. While MRI provides high-quality images, smaller lesions are more difficult to detect and can benefit from contrast agents. Recently, nanoparticles have become an active field of study for imaging. Nanoparticles have shown great potential for use in imaging for several reasons. Their small size (usually 1-200 nanometers) means they are taken up more easily by cells than larger particles. In addition, imaging applications for nanoparticles depend heavily on the ability to target specific tissues, organs, or even cells. Nanoparticles can be designed and surface modified to enhance targeting and increase loading.\(^{1}\) Targeting with nanoparticles can be achieved either through active or passive targeting, which can be achieved through size control. For application to imaging, it is important to use a nanoparticle synthesis method that is scalable, provides size control, and creates nanoparticles with low polydispersity and high loading. The Flash NanoPrecipitation (FNP) method meets these requirements and has been used to encapsulate hydrophobic therapeutics. Recently, the FNP process has been adapted to encapsulate hydrophilic therapeutics such as proteins and peptides using poly(butyl acrylate-b-acrylic acid) (PBA-b-PAA). The first aim was to determine the formulation conditions that affect the size of hydrophilic-encapsulating nanoparticles. The effects of the total mass concentration of materials, percent core, molecular weight, and water in the core were tested on nanoparticles encapsulating polyacrylic acid (PAA) homopolymer. Nanoparticles from ~80-120 nm in diameter with hydrophilic cores and hydrophobic shells were made using the FNP process. As most clinically used MRI contrast agents are gadolinium-based, the second aim of this study was to encapsulate a gadolinium-based contrast agent, gadopentetic acid (Gd-DTPA). Gadolinium-based T1 contrast agents must interact with water in order to be used as contrast agents in MRI so the core of the nanoparticles needed to be hydrophilic. Gd-DTPA was encapsulated at 50% loading and at a size of ~50 nm. These nanoparticles were coated with polystyrene-b-polyethylene glycol (PS-b-PEG), resulting in a final size of ~85 nm. Enhanced passive targeting and higher loading of contrast agents through the use of nanoparticles could improve the use of MRI in clinical and scientific settings.
Extent: 38 pages
Type of Material: Princeton University Senior Theses
Language: en_US
Appears in Collections:Chemical and Biological Engineering, 1931-2016

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