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Authors: Ristroph, Kurt
Advisors: Prud'homme, Robert K
Contributors: Chemical and Biological Engineering Department
Subjects: Pharmaceutical sciences
Chemical engineering
Materials Science
Issue Date: 2021
Publisher: Princeton, NJ : Princeton University
Abstract: The efficient encapsulation of water-soluble biopharmaceuticals (‘biologics’) into micro- and nano-delivery vehicles is essential for their therapeutic success as antibiotics, vaccines, and gene therapies. Encapsulation of biologics using liposomes or water-in-oil-in-water emulsions have struggled to achieve commercial success because they suffer from inefficient encapsulation and poor scalability. The few commercial successes rely heavily on the drug’s specific chemical properties; therefore, the lessons from one formulation are rarely generalizable to other biologics. This variability has hampered the field’s ability to develop methodologies for encapsulating biologics. The result is a patchwork approach for formulation and scaleup that suffers from inefficiencies in (i) independently controlling targets such as vehicle size and charge, payload ratios and loading, drug release rate, and encapsulation efficiency, and (ii) processing at scale. Changing a single target midway through formulation can require restarting the process development. This dissertation describes work aimed at improving the pipeline from drug substance (unformulated biologic) to drug product (formulation at scale) through the development of a nanoformulation strategy applicable across several classes of therapeutics that allows broad control over the targets described above. This research examines (1) the combination of solubility engineering and particle formulation techniques to efficiently encapsulate biologics and water-soluble small molecule drugs into nanocarriers with high loadings; (2) the design and manipulation of internal liquid crystalline structures to control drug release; and (3) the colloidal dynamics in these systems to develop novel large-scale nanocarrier processing operations. Therapeutics formulated and used herein include ecumicin (an antitubercular peptide), polymyxin B (an antimicrobial peptide), and OZ439 and lumefantrine (antimalarial small molecules).
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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