DOI

https://doi.org/10.25772/P3KH-2875

Author ORCID Identifier

https://orcid.org/0000-0002-5486-183X

Defense Date

2020

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Chemical and Life Science Engineering

First Advisor

Christina Tang

Second Advisor

Thomas Roper

Third Advisor

Hu Yang

Fourth Advisor

Christopher Lemmon

Fifth Advisor

Jessika Rojas

Abstract

Taxol, a formulation of paclitaxel (PTX), is one of the most widely used anticancer drugs, particularly for treating recurring ovarian carcinomas following surgery. Clinically, PTX is used in combination with other drugs such as lapatinib (LAP) to increase treatment efficacy. Delivering drug combinations with nanoparticles has the potential to improve chemotherapy outcomes. In this study, we use Flash NanoPrecipitation, a rapid, scalable process to encapsulate weakly hydrophobic drugs (logP in vitro. Encapsulating either PTX or LAP into nanoparticles increases drug potency. When PTX and LAP are co-loaded in the same nanoparticle, they have a synergistic effect that is greater than treating with two single-drug loaded nanoparticles. Furthermore, we examined in vitro sequential delivery of PTX and LAP encapsulated into polymer nanoparticles on ovarian cancer cells. We observed a sequence-dependent cytotoxic effect. These results are promising for establishing sequential drug delivery with nanoparticles as a method for treating ovarian cancer. Building on this work, we demonstrated the potential of encapsulating a hydrophobic PTX prodrug into pH-responsive nanoparticles as a method to enhance drug efficacy and control drug release. Overall, these findings provide the foundation for developing co-encapsulated nanoparticles with controlled drug release as well as methods for improving the drug efficacy of PTX.

Rights

© Shani L. Levit

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-12-2020

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