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Abstract #92580 Published in IGR 22-1
Novel Thiol Containing Hybrid Antioxidant-Nitric Oxide Donor Small Molecules for Treatment of Glaucoma
Amankwa CE; Gondi SR; Dibas A; Weston C; Funk A; Nguyen T; Nguyen KT; Ellis DZ; Acharya SAntioxidants (Basel, Switzerland) 2021; 10:
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 and its active metabolite to scavenge broad-spectrum ROS as well as provide efficient protection from -butyl hydrogen peroxide (TBHP) induced oxidative stress while maintaining NO bioavailability in TM cells. To allow a better drug delivery, a slow release nanosuspension nanoparticles () was prepared, characterized, and tested in dexamethasone induced ocular hypertensive (OHT) mice model for IOP lowering activity. A single topical eye drop of 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.
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Classification:
3.8 Pharmacology (Part of: 3 Laboratory methods)
3.9 Pathophysiology (Part of: 3 Laboratory methods)
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)