Ionic Liquid Pilocarpine Serves as Therapeutic Cosolvent and Permeation Enhancer for Glaucoma Medication

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dc.contributor.authorTrital, Ashish
dc.contributor.authorXu, Lei
dc.contributor.authorAtes, Burhan
dc.contributor.authorWang, Tzu-Chen
dc.contributor.authorMani, Vimalin
dc.contributor.authorYang, Hu
dc.date.accessioned2026-04-04T13:34:42Z
dc.date.available2026-04-04T13:34:42Z
dc.date.issued2026
dc.departmentİnönü Üniversitesi
dc.description.abstractThe efficacy of hydrophobic ocular drugs is significantly hindered by their low bioavailability, for which poor water solubility is a major contributing factor. In this work, we synthesized pilocarpine-derived ionic liquid [Pilo-OEG] Cl (PO) and evaluated its cosolvent properties for the codelivery of the hydrophobic antiglaucoma drug brimonidine (BM) for glaucoma therapy. Pilocarpine was quaternized with 2-[2-(2-chloroethoxy)ethoxy] ethanol in a one-pot reaction to yield PO, and its structure was confirmed using 1H NMR and FT-IR spectroscopy methods and further characterized for its rheological property and thermal stability. The HET-CAM assay and cell viability study showed that PO was nonirritating and cytocompatible with trabecular meshwork cells. As a cosolvent, PO increased the solubility of BM and shifted its logP toward hydrophilicity and increased its ex vivo corneal permeability to be 2.7-fold higher. Following topical administration, a single dose of the PO:BM formulation decreased intraocular pressure (IOP) in rats and effectively maintained the IOP reduction for 48 h, whereas the IOP in the rats topically treated with brimonidine tartrate returned to the baseline in less than 12 h. A sustained IOP reduction over 7 days was achieved in a multiple-dose experiment, with efficacy still observed on day 8 by PO: BM. By combining intrinsic muscarinic activity with potent cosolvent properties, PO ionic liquid addresses the solubility and bioavailability challenges of hydrophobic drugs (BM) in a simple formulation (PO:BM), presenting a promising next-generation therapy for the treatment of glaucoma.
dc.description.sponsorshipClinical Center [R01EY035088]
dc.description.sponsorshipThis study was supported, in part, by the National Institute of Health (NIH) R01EY035088 (H. Yang).
dc.identifier.doi10.1021/acsptsci.5c00799
dc.identifier.endpage735
dc.identifier.issn2575-9108
dc.identifier.issue3
dc.identifier.pmid41852625
dc.identifier.scopus2-s2.0-105032811632
dc.identifier.scopusqualityQ1
dc.identifier.startpage725
dc.identifier.urihttps://doi.org/10.1021/acsptsci.5c00799
dc.identifier.urihttps://hdl.handle.net/11616/109351
dc.identifier.volume9
dc.identifier.wosWOS:001706633600001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherAmer Chemical Soc
dc.relation.ispartofAcs Pharmacology & Translational Science
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250329
dc.subjectpilocarpine
dc.subject[Pilo-OEG]Cl
dc.subjectionic liquid
dc.subjectviscous liquid
dc.subjectcosolvent
dc.subjectantiglaucoma drugs
dc.titleIonic Liquid Pilocarpine Serves as Therapeutic Cosolvent and Permeation Enhancer for Glaucoma Medication
dc.typeArticle

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