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Title: Therapeutic Nanocarriers for Enhanced Drug Delivery: from Laboratory-Scale Formulation to Clinical-Scale Production
Authors: Tian, Chang
Advisors: Prud'homme, Robert K
Contributors: Chemical and Biological Engineering Department
Keywords: drug delivery
drug development
Flash NanoPrecipitation
Subjects: Chemical engineering
Pharmaceutical sciences
Issue Date: 2020
Publisher: Princeton, NJ : Princeton University
Abstract: This thesis describes studies in the development of therapeutic nanoparticles to achieve enhanced drug delivery, starting from formulation design to scale-up production and processing. Polymeric NPs can encapsulate hydrophobic active pharmaceutical ingredients in their amorphous form and at the same time maintain a high surface area to volume ratio, so as to increase bioavailability in drug delivery. Flash NanoPrecipitation is the main technique to be applied in this thesis for the formation of nanoparticles. It is a one-step and scalable method. This technique is further developed in this thesis to better encapsulate different drug molecules of various hydrophobicity and eventually achieve a continuous scale-up production for commercialization purpose. The work presented herein is divided into four main parts based on four different projects where I have spent the majority of my Ph.D. career. In a project working on dihydromyricetin as a hangover prevention drug, we demonstrate the flexibility of Flash NanoPrecipitation formulations in encapsulating less hydrophobic drugs. In a project working on lumefantrine as a cure for malaria, we successfully achieve translational development in terms of scale-up production and processing of nanoparticles. In a project working on HIV pre-exposure prophylaxis, we design responsive foams as a nanoparticle rectal dosage vehicle. Last but not least, we develop mathematical models to describe nanoparticle adsorption and structural rearrangement at an interface, which involves a fundamental discussion of some of the most commonly seen phenomenon. In summary, the four projects listed in this dissertation not only involve different formulations of therapeutic nanoparticles for different diseases, but also emphasize on different stages of the research of nanomedicine, from the initial encapsulation process to scale-up production and eventually final dosage form. With all the formulation and processing methods developed in this dissertation, we have successfully bridged the gap between Flash NanoPrecipitation as an innovative nanoparticle synthesis technology starting in the lab and its subsequent formulation evolvement, to align with different chemical natures of drugs to be encapsulated as well as requirements of industrial-level production. This work will further inspire scientists working in the field of nanomedicine to facilitate the application of Flash NanoPrecipitation in a broader perspective in industry.
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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