Date of Award

5-23-2019

Document Type

Thesis

Degree Name

Bachelor of Science (B.S.) in Biochemistry and University Honors

Department

Biochemistry

First Advisor

Adam Alani

Subjects

Glioblastoma multiforme, Brain -- Cancer, Cyclodextrins -- Physiological effect, Drug delivery systems

DOI

10.15760/honors.694

Abstract

Glioblastoma multiforme (GBM) is the most common type of high-grade glioma and accounts for as much as 50% of all primary brain tumors. With the current standard of care, survival of GBM patients remains poor at 15 months after diagnosis. In this study, the antiproliferative effects of a novel oxazine-4 derivative called 0108 were examined. Delivery of 0108 was accomplished via complexation with (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) to form 0108CD. The association constant, Ka, of 0108CD was determined and stability of 0108CD formulations made with 1, 2.5, 5, 7.5, and 10% HP-β-CD were assessed over 24, 48, and 72 hours. The in vitro toxicity of 0108 and 0108CD was quantified via IC50 in U87-MG, U118-MG, SF298, and SF268 cell lines. The effects of 0108 on cell phase were examined in U87-MG.

The 5% HP-β-CD formulation was established as the optimal 0108CD treatment based on maximum 0108 encapsulation without HP-β-CD oversaturation. Stability of the 5% HP-β-CD formulation decreased after 24 hours. Incorporating 0108 in a HP-β-CD vesicle did not change the potency of the drug in SF295-MG and U118-MG, and increased its potency in U87-MG and SF268-MG. 0108 treatment at the highest dose showed a time-independent increase in the number of cells in G0/G1 and S phases and a decrease in G2/M phase.

Persistent Identifier

https://archives.pdx.edu/ds/psu/28728

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