Degree

Doctor of Philosophy (PhD)

Department

Chemistry - Rivas Group

Document Type

Dissertation

Abstract

Poor physicochemical properties combined with pharmacokinetics and biodistribution of promising steroidal molecules have hampered clinical advancement to potentially treat cancer effectively. Selective and effective treatment of cancer would improve the quality of life and extend life in various deadly cancer subtypes such as triple negative breast cancer which leads to 150,000 deaths per year.1,2 Therefore, there is an urgent need to develop analytical methods to improve the physicochemical properties of these compounds.

Liposomes are amphiphilic molecules that can serve as encapsulating systems to selectively target localized solid tumors, improving the effectiveness of treatment. The development of a general liposomal delivery system for steroidal natural products offers the opportunity to observe the outcomes of breast cancer cell research and potentially improve therapeutic efficacy is the focus of the work presented. While the capacity for the development of liposomal drug delivery systems is great, there is a need for a significant understanding of the microenvironment of the targeted area.

Presented herein are analytical methods, both developed and adaptive, which have been used to investigate the encapsulation and release of bioactive steroidal natural products at the targeted site. Natural products are carbon-based and present challenges surrounding solubility, permeability, and bioavailability. This dissertation is focused on utilizing natural products in conjunction with FDA-approved lipids such as dioleoyl phosphatidylcholine (DOPC) and dipalmitoyl phosphatidyl (DPPC) in addition to a synthesized organic compound from the Rivas Group, FR-M002, and ergosterol (ERG).

The aims of this work are (1) to develop general nanosized DDSs from liposomes and synthesized organic compounds for the delivery of bioactive steroidal natural product molecules and (2) to investigate the properties of these DDS (size distribution, stability, and cellular uptake).

Preliminary studies using these model systems to assess the feasibility of the generation of these DDSs are presented herein. These DDSs are characterized by using dynamic light scattering (DLS) and transmission electron microscopy (TEM). DLS will provide insight into the nanoparticles' polydispersity of size distribution while TEM will image the sample and provide physical information using a beam of electrons to create an image of the sample highlighting size and morphology. Introduced here are the findings and the significance of this work.

Date

6-24-2024

Committee Chair

Rivas, Fatima

DOI

https://doi.org/10.31390/gradschool_dissertations.6511

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Available for download on Thursday, June 24, 2027

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