advertisement
Abstract #105779 Published in IGR 23-3
Ionic Liquid Pilocarpine Analog as an Antiglaucoma Drug Candidate
Wang J; Li B; Tang J; Qiu L; Qiao X; Xu N; Yang HACS pharmacology & translational science 2022; 5: 752-760
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 H 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.
College of Biomedical Engineering, Sichuan University, Chengdu, Sichuan 610065, China.
Full article