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    Engineered Multifunctional Drug-Loaded Dendrimer Nanoparticles for Glaucoma: Triple Mechanism via Antioxidant Activity, Iron Chelation, and Enhanced Ocular Transport
    (Amer Chemical Soc, 2025) Ates, Burhan; Trital, Ashish; Mani, Vimalin Jeyalatha; Xu, Lei; Kenlee, Jonathan; Ercal, Nuran; Yang, Hu
    In this study, we developed multifunctional nanoparticles based on polyamidoamine (PAMAM) dendrimers functionalized with caffeic acid (CA) and poly(ethylene glycol) maleimide (PEGM) for the topical delivery of hydrophobic antiglaucoma drugs brimonidine (BM) and betaxolol (BX). The PAMAM-CA and PAMAM-CA-PEGM conjugates exhibited antioxidant and iron-chelating activities in a dose-dependent manner. BM- and BX-loaded dendrimer nanoparticles produced using a multi-inlet vortex mixer showed uniform spherical morphology (similar to 80 nm by TEM) and hydrated sizes of similar to 135-144 nm by DLS. Both nanoformulations demonstrated high cytocompatibility with human corneal epithelial cells and were nonirritant in the HET-CAM assay, with PEGM further improving cytocompatibility. Drug release was sustained for 8 h. Ex vivo corneal permeation studies revealed significantly enhanced drug transport, with PAMAM-CA and PAMAM-CA-PEGM nanoparticles achieving approximately 2- and 3-fold higher permeation, respectively, compared to commercial formulations. Conjugation of CA within our formulations effectively promoted the removal of ferric ions from the surrounding environment. Both PAMAM-CA and PAMAM-CA-PEGM nanoparticles exhibited concentration-dependent antioxidant activity comparable to that of CA. These findings suggest the potential of this multifunctional dendrimer-based nanoparticle system as an innovative strategy for glaucoma medication.
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    The protective effect of N-acetylcysteine amide against paraquat-induced neurotoxicity
    (Tubitak Scientific & Technological Research Council Turkey, 2019) Ates, Burhan; Vardi, Nigar; Parlakpinar, Hakan; Karaaslan, Merve Goksin; Yilmaz, Ismet; Ercal, Nuran
    N-acetylcysteine amide (NACA) is a new antioxidant molecule with powerful radical scavenging properties. The aim of this study was to investigate neuroprotective effects of NACA against paraquat (PQ) toxicity in the midbrains of rats by using motor coordination tests and biochemical and histological analysis. Thirty adult Wistar albino rats were divided into three groups: Group 1: control (n = 10), Group 2: PQ (10 mg/kg) (n = 10), and Group 3: PQ (10 mg/kg) + NACA (100 mg/kg) (n = 10). NACA was administrated intraperitoneally 30 min before PQ injection. Performance was measured for a period of 28 days. The rotarod and accelerod tests were performed prior to and after the experimental period. After the experimental period, rats were sacrificed and midbrain tissues were removed. According to biochemical data, malondialdehyde levels exhibited a significant increase (P < 0.05) when the PQ group was compared to the control group, whereas the NACA-treated group showed a significant decline (P < 0.05). The total glutathione levels (P < 0.01) and the glutathione peroxidase and butyrylcholinesterase activities (P < 0.05) in the NACA treatment group were significantly raised compared with the PQ group. The main finding in the rotarod and accelerod tests was that the PQ + NACA group had improved motor coordination functions, whereas the PQ group had lost motor coordination (P < 0.05). Our histological data were also outstanding and were consistent with biochemical and motor coordination results in terms of the protective role of NACA against PQ-induced neurotoxicity.