Doctoral Dissertations

Author

Justin Beltz

Keywords and Phrases

Antioxidants; Cataract; Drug Delivery; Nanodiamond; Oxidative Stress; Tiopronin; Aging

Abstract

”There is a growing demand for non-surgical means of cataract treatment. This dissertation presents three bodies of work that reflect the early-stage development of eye drop formulations aimed at delaying cataract progression. These formulations consist of the antioxidant 2-mercaptopropionylglycine (MPG) loaded onto nanodiamond particles.

Cataractogenesis is linked to oxidative damage to lens proteins. To investigate the potential of MPG for protection against oxidative damage, A549 cells were incubated in 0.6 mM tert-butylhydroperoxide (tBHP). Cells exposed to tBHP without MPG exhibited elevated levels of reactive oxygen species, which led to the depletion of the vital antioxidant glutathione and, ultimately, apoptosis. Co-administration of 5 mM MPG protected cells from tBHP-induced damage, resulting in maintenance of cell viability.

To monitor the uptake and fate of MPG in the eye, a rapid, high sensitivity HPLC method was developed for the analysis of MPG and its metabolite, 2-mercaptopropionic acid, in ocular tissues. Method validation experiments demonstrated the reliability of this method for quantifying MPG uptake and evaluating drug delivery strategies.

Achieving effective drug concentrations in the lens poses a major challenge. Nanodiamond is biocompatible, and its surface chemistry can be tailored to specific applications. Thus, it is emerging as a candidate of interest for drug delivery. Nanodiamond surfaces were functionalized with carboxyl (ND-COOH), hydroxyl (ND- OH), and amino (ND-NH2) groups to investigate the effect of ND surface chemistry on adsorption and release of MPG. The ND-NH2 exhibited the highest adsorption capacity, but the ND-OH was the most effective for sustained release”--Abstract, page iv.

Advisor(s)

Ercal, Nuran

Committee Member(s)

Woelk, Klaus
Sotiriou-Leventis, Lia
Shi, Honglan
Huang, Yue-Wern

Department(s)

Chemistry

Degree Name

Ph. D. in Chemistry

Comments

This research was made possible by the Richard K. Vitek/FCR Endowment.

Publisher

Missouri University of Science and Technology

Publication Date

Fall 2020

Journal article titles appearing in thesis/dissertation

  • Protective effects of tiopronin on oxidatively challenged human lung carcinoma epithelial cells (A549)
  • Simultaneous determination of tiopronin and its primary metabolite in plasma and ocular tissues by HPLC
  • Effect of nanodiamond surface chemistry on adsorption and release of tiopronin

Pagination

xv, 98 pages

Note about bibliography

Includes bibliographic references.

Rights

© 2020 Justin Edward Beltz, All rights reserved.

Document Type

Dissertation - Open Access

File Type

text

Language

English

Thesis Number

T 11775

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