Date of Award

Fall 12-15-2015

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Dr. Ishrat Khan

Second Advisor

Dr. James Reed

Third Advisor

Dr. Michelle Gaines

Abstract

An inclusion complex between β-cyclodextrin and insoluble guest compounds has been reported by several researchers. The main purpose of forming an inclusion complex between β-CD and sparingly soluble guests is to enhance the guest’s solubility and mask its undesirable properties. Preliminary studies have shown that when conjugated with target-specific moieties, these inclusion complexes can be used in pharmaceutical applications for drug delivery. β-Sitosterol, a plant sterol, has been well documented to reduce tumor cell growth and migration as well as exhibit apoptotic characteristics. An issue with this plant sterol and most pharmaceutical compounds is their lack of solubility. In this study, we propose that an inclusion complex will enhance the solubility of this sterol and change the physicochemical properties of the sparingly soluble guest. We first prepared the β-CD:β-Sitosterol inclusion complex and characterized the samples in both solid and solution state. The complex was characterized using FT-IR, DSC, SEM and NMR. IR studies of the inclusion complex and physical mixture revealed changes in the characteristic peaks of the inclusion complex suggestive of the formation of a new compound. 1HNMR studies revealed an upfield resonance shift of β-CD internal protons (H3 and H5) as an equal molar ratio of β-Sitosterol is introduced into the β-CD mixture. 2D NOESY NMR studies suggest that the initial sites of interaction of β-CD and β-Sitosterol occur between the aliphatic tail of β-Sitosterol and H3 of β-CD. 2D ROESY NMR reveals that the cyclic head of β-Sitosterol also interacts with the cavity of β-CD suggesting that β-Sitosterol may be completely encapsulated inside β-CD’s cavity. From these initial studies, we hypothesize that the β-CD-PEG-FA will facilitate absorption of β-Sitosterol and increase the drug delivery vehicle’s solubility as a whole. Since most tumor cells over-express folic acid, inclusion of folic acid in the construct of the vehicle will direct these sterols to tumor sites. β-cyclodextrin-PEG, a precursor to the bio-conjugate for antitumor delivery of sterols, was synthesized and characterized.

Dissertation new 6.23.15.docx (4987 kB)
Janet Cowins Dissertation_1

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