2. Academic Validation
  3. Ionic Liquid Pilocarpine Analog as an Antiglaucoma Drug Candidate

Ionic Liquid Pilocarpine Analog as an Antiglaucoma Drug Candidate

  • ACS Pharmacol Transl Sci. 2022 Jul 8;5(9):752-760. doi: 10.1021/acsptsci.2c00024.
Juan Wang 1,  Boxuan Li 2,  Jing Tang 3,  Li Qiu 1,  Xin Qiao 1,  Na Xu 1,  Hu Yang 4
Affiliations

Affiliations

  • 1 College of Biomedical Engineering, Sichuan University, Chengdu, Sichuan 610065, China.
  • 2 Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China.
  • 3 Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
  • 4 Linda and Bipin Doshi Department of Chemical and Biochemical Engineering, Missouri University of Science and Technology, Rolla, Missouri 65409, United States.
PMID: 36110370 DOI: 10.1021/acsptsci.2c00024
Abstract

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.

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