Novel Thiol Containing Hybrid Antioxidant-Nitric Oxide Donor Small Molecules for Treatment of Glaucoma

Date

2021-04-08

Authors

Amankwa, Charles E.
Gondi, Sudershan R.
Dibas, Adnan Dibas
Weston, Courtney
Funk, Arlene
Nguyen, Tam
Nguyen, Kytai T.
Ellis, Dorette Z.
Acharya, Suchismita

ORCID

0000-0002-1120-7053 (Amankwa, Charles E.)

Journal Title

Journal ISSN

Volume Title

Publisher

MDPI

Abstract

Oxidative stress induced death and dysregulation of trabecular meshwork (TM) cells contribute to the increased intraocular pressure (IOP) in primary open angle (POAG) glaucoma patients. POAG is one of the major causes of irreversible vision loss worldwide. Nitric oxide (NO), a small gas molecule, has demonstrated IOP lowering activity in glaucoma by increasing aqueous humor outflow and relaxing TM. Glaucomatous pathology is associated with decreased antioxidant enzyme levels in ocular tissues causing increased reactive oxygen species (ROS) production that reduce the bioavailability of NO. Here, we designed, synthesized, and conducted in vitro studies of novel second-generation sulfur containing hybrid NO donor-antioxidants SA-9 and its active metabolite SA-10 to scavenge broad-spectrum ROS as well as provide efficient protection from t-butyl hydrogen peroxide (TBHP) induced oxidative stress while maintaining NO bioavailability in TM cells. To allow a better drug delivery, a slow release nanosuspension SA-9 nanoparticles (SA-9 NPs) was prepared, characterized, and tested in dexamethasone induced ocular hypertensive (OHT) mice model for IOP lowering activity. A single topical eye drop of SA-9 NPs significantly lowered IOP (61%) at 3 h post-dose, with the effect lasting up to 72 h. This class of molecule has high potential to be useful for treatment of glaucoma.

Description

Citation

Amankwa, C. E., Gondi, S. R., Dibas, A., Weston, C., Funk, A., Nguyen, T., Nguyen, K. T., Ellis, D. Z., & Acharya, S. (2021). Novel Thiol Containing Hybrid Antioxidant-Nitric Oxide Donor Small Molecules for Treatment of Glaucoma. Antioxidants (Basel, Switzerland), 10(4), 575. https://doi.org/10.3390/antiox10040575

Rights

© 2021 by the authors.

License

Attribution 4.0 International (CC BY 4.0)