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Title: Polymeric Nanoparticles and Microparticles for the Delivery of Hydrophobic and Hydrophilic Therapeutics
Authors: Pagels, Robert Frederick
Advisors: Prud'homme, Robert K
Contributors: Chemical and Biological Engineering Department
Keywords: biologic
drug delivery
Subjects: Chemical engineering
Polymer chemistry
Issue Date: 2018
Publisher: Princeton, NJ : Princeton University
Abstract: Polymeric particle formulations can improve the therapeutic performance of two distinct drug classes: hydrophobic small molecules and hydrophilic biologic macromolecules. Nanoparticle formulations of hydrophobic drugs can increase the dissolution rate, improve bioavailability, and target the therapeutic to tissues of interest. Nanoparticle and microparticle formulations of biologics can slowly release the encapsulated drug over time, reducing the required injection frequency and increasing patient comfort and compliance. While particle formulations can benefit both hydrophobic and hydrophilic therapeutics, there currently is not a platform technology capable of encapsulating drugs of both classes. The work presented herein applies the Flash NanoPrecipitation (FNP) process to the formulation of both water-insoluble (Part I) and water-soluble (Part II) materials. FNP has traditionally been used to produce nanoparticles of hydrophobic therapeutics. In Part I of this dissertation, a kinetic model of the nanoparticle assembly process during FNP was produced. This model can be used to predict and optimize formulations of new hydrophobic drugs based on the required particle size and drug loading. In addition to particle size, the effect of the FNP process parameters on the resulting particle surface properties was also characterized. Finally, a simple synthesis method for producing targetable stabilizing block copolymers for use in FNP was developed. In Part II, the FNP process was inverted (iFNP) to allow for the encapsulation of hydrophilic molecules. The new iFNP process was demonstrated on a variety of model drugs, and the methods to control nanoparticle size were established. The resulting “inverted” particles made by iFNP were either coated with a second polymer layer for use as circulating nanoparticles, or assembled into larger microparticles. New biodegradable block copolymers for use in the iFNP process were synthesized, characterized, and applied to the formulation of a model therapeutic peptide. Microparticles containing the model peptide were produced by iFNP with loadings five to ten times higher than those achievable with other technologies. Release of the peptide was demonstrated over more than a month-long period. In summary, this dissertation expands the applicability of the FNP platform technology, enabling new nanoparticle and microparticle formulations of therapeutics.
Alternate format: The Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the library's main catalog:
Type of Material: Academic dissertations (Ph.D.)
Language: en
Appears in Collections:Chemical and Biological Engineering

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