First Advisor

Adam Alani

Date of Award

5-23-2019

Document Type

Thesis

Degree Name

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

Department

Chemistry

Subjects

Cyclodextrins, Drug delivery systems, Glioblastoma multiforme

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.

Rights

In Copyright. URI: http://rightsstatements.org/vocab/InC/1.0/ This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).

Persistent Identifier

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

Download

Share

COinS