Graduation Date

Spring 5-7-2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Pharmaceutical Sciences

First Advisor

David Oupický

Abstract

Local pulmonary administration of therapeutic siRNA represents a promising approach to the treatment of lung fibrosis, which is currently hampered by inefficient delivery. Pancreatic cancer (PC) is a fatal human cancer whose progression is highly dependent on the nervous tumor microenvironment. siRNA delivery has been well studied as a promising therapeutic agent for several disease, including the pulmonary fibrosis and cancer. Perfluorocarbon nanoemulsions have been studied in the treatment of various diseases as drug delivery systems. We report development of perfluorooctylbromide (PFOB) nanoemulsions as a platform to facilitate delivery and penetration of a therapeutic siRNA to pulmonary fibrosis lung and orthotopic pancreatic tumors. PCX@PFOB emulsion, which contained the polymeric CXCR4 antagonist PCX with PFOB, is a dual functional emulsion to inhibit CXCR4 and deliver siRNA. This dissertation hypothesized that inhibition of CXCR4 by PCX@PFOB emulsion combined with siRNA delivery cooperatively enhances the pulmonary fibrosis and PC treatment.

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