Keywords and Phrases
Antioxidants; Cataract; Drug Delivery; Nanodiamond; Oxidative Stress; Tiopronin; Aging
”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.
Ph. D. in Chemistry
Missouri University of Science and Technology
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
xv, 98 pages
© 2020 Justin Edward Beltz, All rights reserved.
Dissertation - Open Access
Beltz, Justin, "Tools to evaluate nanodiamond-mediated delivery of tiopronin for cataract prevention" (2020). Doctoral Dissertations. 2946.