Novel Thiol Containing Hybrid Antioxidant-Nitric Oxide Donor Small Molecules for Treatment of Glaucoma.
Novel Thiol Containing Hybrid Antioxidant-Nitric Oxide Donor Small Molecules for Treatment of Glaucoma.
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DOI：
10.3390/antiox10040575
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发表时间：
2021-04-08
期刊：
影响因子：
--
通讯作者：
Acharya S
中科院分区：
文献类型：
--
作者：
Amankwa CE;Gondi SR;Dibas A;Weston C;Funk A;Nguyen T;Nguyen KT;Ellis DZ;Acharya S
原发性开角型青光眼患者中，氧化应激诱导的小梁网（TM）细胞死亡和失调导致眼内压（IOP）升高。POAG是世界范围内不可逆视力丧失的主要原因之一。一氧化氮（NO）是一种小分子气体，通过增加房水流出量和松弛TM来降低青光眼的IOP。青光眼病理与眼组织中抗氧化酶水平降低有关，导致活性氧（ROS）产生增加，从而降低NO的生物利用度。并进行了新的第二代含硫杂合NO供体-抗氧化剂SA-9及其活性代谢物SA-10的体外研究，以抑制广谱ROS，并提供有效的保护，丁基过氧化氢（TBHP）诱导氧化应激，同时维持TM细胞中NO的生物利用度。为了允许更好的药物递送，制备、表征了缓释纳米悬浮液SA-9纳米颗粒（SA-9 NP），并在地塞米松诱导的高眼压（OHT）小鼠模型中测试了IOP降低活性。SA-9 NP的单次局部滴眼剂在给药后3 h显著降低IOP（61%），效果持续长达72 h。这类分子具有用于治疗青光眼的高潜力。
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.
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影响因子：
4.6
作者：
Le DQ;Kuriakose AE;Nguyen DX;Nguyen KT;Acharya S
通讯作者：
Acharya S
影响因子：
3.4
作者：
Minhas G;Morishita R;Anand A
通讯作者：
Anand A
影响因子：
13.7
作者：
Olthoff, CMG;Schouten, JSAG;Webers, CAB
通讯作者：
Webers, CAB
影响因子：
4.4
作者：
Ellis, Dorette Z.;Dismuke, William M.;Chokshi, Binna M.
通讯作者：
Chokshi, Binna M.
拉坦前列烯Bunod在青光眼治疗中的批判性评估。
DOI：
10.2147/opth.s103985
发表时间：
2016
期刊：
Clinical ophthalmology (Auckland, N.Z.)
影响因子：
--
作者：
Garcia GA;Ngai P;Mosaed S;Lin KY
通讯作者：
Lin KY