Novel Thiol Containing Hybrid Antioxidant-Nitric Oxide Donor Small Molecules for Treatment of Glaucoma
| Autor: | Suchismita Acharya, Adnan Dibas, Arlene Funk, Tam Nguyen, Kytai T. Nguyen, Dorette Z. Ellis, Charles Amankwa, Courtney Weston, Sudershan R. Gondi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Intraocular pressure Antioxidant Open angle glaucoma genetic structures Physiology medicine.medical_treatment Clinical Biochemistry Glaucoma Pharmacology superoxide radical medicine.disease_cause Biochemistry Article Nitric oxide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine nitric oxide medicine Molecular Biology intra-ocular pressure nanosuspension chemistry.chemical_classification Reactive oxygen species lcsh:RM1-950 Cell Biology medicine.disease eye diseases lcsh:Therapeutics. Pharmacology 030104 developmental biology medicine.anatomical_structure glaucoma chemistry hybrid small molecule 030221 ophthalmology & optometry Trabecular meshwork sense organs Oxidative stress |
| Zdroj: | Antioxidants Volume 10 Issue 4 Antioxidants, Vol 10, Iss 575, p 575 (2021) |
| ISSN: | 2076-3921 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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