Ionic liquid pilocarpine analog [Pilo-OEG]Cl, the first-of-its-kind ionic liquid antiglaucoma drug candidate, is synthesized and reported. To synthesize [Pilo-OEG]Cl, pilocarpine was reacted with the oligo-polyethylene glycol chloride, 2-[2-(2-chloroethoxy)ethoxy] ethanol, to form an ionic liquid molecule with an imidazole cation and a chloride anion. The chemical structure of [Pilo-OEG]Cl was confirmed with 1H NMR spectroscopy. Compared with pilocarpine (Pilo) and pilocarpine hydrochloride (PiloHCl), [Pilo-OEG]Cl has improved structural stability according to pH measurements and LC-MS analysis. The corneal permeability coefficient of [Pilo-OEG]Cl is 2-fold higher than that of Pilo and 8-fold higher than that of PiloHCl. [Pilo-OEG]Cl does not show apparent toxicity to human corneal epithelial cells over a broad range of concentrations up to 50 mM. The in vivo efficacy of PiloHCl and [Pilo-OEG]Cl was tested in normotensive adult Brown Norway female rats. [Pilo-OEG]Cl is found to be more potent than PiloHCl in lowering the intraocular pressure (IOP). [Pilo-OEG]Cl is more cytocompatible than PiloHCl based on the in vitro ELISA and hemolysis tests and in vivo histological analysis. Taken together, [Pilo-OEG]Cl has enhanced stability, corneal permeability, better IOP-lowering efficacy, and improved biocompatibility, thus making it a promising new drug candidate for antiglaucoma therapy. Transforming old antiglaucoma drugs to pharmaceutically active ionic liquids represents an innovative approach to developing glaucoma medications.
J. Wang et al., "Ionic Liquid Pilocarpine Analog as an Antiglaucoma Drug Candidate," ACS Pharmacology and Translational Science, vol. 5, no. 9, pp. 752 - 760, American Chemical Society, Sep 2022.
The definitive version is available at https://doi.org/10.1021/acsptsci.2c00024
Chemical and Biochemical Engineering
Keywords and Phrases
corneal permeability; glaucoma; intraocular pressure reduction; ionic liquid; pilocarpine
International Standard Serial Number (ISSN)
Article - Journal
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09 Sep 2022
National Institutes of Health, Grant R01EY024072