Semester

Summer

Date of Graduation

2021

Document Type

Dissertation

Degree Type

PhD

College

School of Pharmacy

Department

Pharmaceutical Sciences

Committee Chair

Paul R. Lockman

Committee Member

R. Alfredo C. Siochi

Committee Member

Werner Geldenhuys

Committee Member

Lori A. Hazlehurst

Committee Member

Marina Galvez

Abstract

This dissertation (a) provided an in depth literature review of methods to disrupt the BBB/BTB and improve therapeutic distribution to brain tumors, (b) evaluated the use of azacitidine as a single agent therapy for the treatment of brain metastasis of breast cancer and a potential molecular mechanism by which brain tropic cells are sensitized to hypomethylating agents, (c) determined the impact cannabidiol has on P-glycoprotein mediated efflux at the blood-brain barrier and its potential for use as a single agent treatment for metastatic brain tumors, (d) developed a preclinical radiation therapy protocol for use in small animals and in vitro systems, (e) evaluated the impact radiation therapy has on blood-brain barrier integrity in normal and pathological brain, and (f) provided a discussion on the mathematical models used to evaluate blood-brain barrier pharmacokinetics in both normal and pathophysiological conditions.

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