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Design, Formation, and Characterization of Polymeric Nanoparticles for Drug Delivery

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Title: Design, Formation, and Characterization of Polymeric Nanoparticles for Drug Delivery
Author(s): Szymusiak, Magdalena
Advisor(s): Liu, Ying
Contributor(s): Nitsche, Ludwig C.; Wedgewood, Lewis E.; Perez-Salas, Ursula; Wang, Zaijie J.
Department / Program: Chemical Engineering
Graduate Major: Chemical Engineering
Degree Granting Institution: University of Illinois at Chicago
Degree: PhD, Doctor of Philosophy
Genre: Doctoral
Subject(s): Drug delivery Polymeric nanoparticles Flash precipitation and drying Bioavailability Small-angle x-ray scattering
Abstract: Recent developments in the field of nanotechnology have shown nanoparticles’ attractive potential for enhanced drug bioavailability and functionality. Although the research of developing and producing nanoparticle-based medicines has undergone rapid expansion, numerous challenges lie ahead in terms of long-term stability, reproducibility, and scalability, being major limiting factors for their direct clinical translation. We have developed an integrated process of flash nanoprecipitation (FNP) in a custom-made multi inlet vortex mixer (MIVM) and freeze/spray drying (process referred to as Flash Precipitation and Drying - FPaD) in order to achieve high drug loading and long-term stability of polymeric nanoparticles encapsulating hydrophobic compounds. The process was first developed for a model hydrophobic compound – curcumin, and later applied and optimized for a variety of other hydrophobic compounds – both small-molecule drugs and macromolecule peptides. The effects of the physical parameters such as polymer to drug ratio and the nanoparticle to excipient ratio were investigated in order to achieve optimized formulations. The viability of the nanoformulations was verified in mice and bioavailability of curcumin and its major metabolite in plasma and central nervous system (CNS) of mice after oral delivery of nano-curcumin (curcumin encapsulated in PLGA nanoparticles) was precisely measured. A 20-fold reduction of dose requirement was observed when compared with the unformulated drug to achieve similar plasma and CNS tissue concentrations. The structures of a wide variety of polymeric micelles composed of simple linear diblock copolymers and novel brush amphiphilies as potential drug carriers were characterized by using small-angle x-ray scattering (SAXS). This method offers more benefits of polymeric nanoparticle characterization over conventional techniques such as dynamic light scattering (DLS) or transmission electron microscopy (TEM), providing in situ detailed internal features of the nanoparticles (i.e. core radius, shell thickness, and aggregation number). Furthermore, surface modification of nanoparticles for enhanced functionality and targeted drug delivery was demonstrated by a facile conjugation of a therapeutic procoagulant hydrophilic polymer, polyphosphate (polyP), on the surface of gold nanoparticles (GNPs). The polyP-GNPs were found to be markedly superior contact-pathway activators compared to molecularly dissolved, platelet-sized polyP (of equivalent polymer chain length).
Issue Date: 2016-10-19
Genre: thesis
URI: http://hdl.handle.net/10027/21281
Rights Information: Copyright 2016 Magdalena Szymusiak
Date Available in INDIGO: 2018-10-20
Date Deposited: 2016-08
 

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