Engineered Multifunctional Drug-Loaded Dendrimer Nanoparticles for Glaucoma: Triple Mechanism via Antioxidant Activity, Iron Chelation, and Enhanced Ocular Transport

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dc.contributor.authorAtes, Burhan
dc.contributor.authorTrital, Ashish
dc.contributor.authorMani, Vimalin Jeyalatha
dc.contributor.authorXu, Lei
dc.contributor.authorKenlee, Jonathan
dc.contributor.authorErcal, Nuran
dc.contributor.authorYang, Hu
dc.date.accessioned2026-04-04T13:34:44Z
dc.date.available2026-04-04T13:34:44Z
dc.date.issued2025
dc.departmentİnönü Üniversitesi
dc.description.abstractIn 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.
dc.description.sponsorshipNational Institutes of Health [R01EY035088]
dc.description.sponsorshipThis study was supported, in part, by the National Institutes of Health R01EY035088 (HY).
dc.identifier.doi10.1021/acs.biomac.5c01704
dc.identifier.endpage8738
dc.identifier.issn1525-7797
dc.identifier.issn1526-4602
dc.identifier.issue12
dc.identifier.orcid0000-0001-6080-229X
dc.identifier.orcid0009-0008-3181-7028
dc.identifier.orcid0000-0003-3030-004X
dc.identifier.pmid41289503
dc.identifier.scopus2-s2.0-105024252555
dc.identifier.scopusqualityQ1
dc.identifier.startpage8726
dc.identifier.urihttps://doi.org/10.1021/acs.biomac.5c01704
dc.identifier.urihttps://hdl.handle.net/11616/109373
dc.identifier.volume26
dc.identifier.wosWOS:001623186000001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherAmer Chemical Soc
dc.relation.ispartofBiomacromolecules
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20250329
dc.subjectDelivery-System
dc.subjectAssociation
dc.subjectQuantification
dc.subjectPrevalence
dc.subjectMembrane
dc.subjectModel
dc.subjectGel
dc.titleEngineered Multifunctional Drug-Loaded Dendrimer Nanoparticles for Glaucoma: Triple Mechanism via Antioxidant Activity, Iron Chelation, and Enhanced Ocular Transport
dc.typeArticle

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