Crown Ethers: Novel Permeability Enhancers for Ocular Drug Delivery?

• DOI: 10.1021/acs.molpharmaceut.7b00556
• Publication Date: 2017-08-21T14:32:49Z
• Authors: Peter W. J. Morrison; Natalia N. Porfir...; Sukhmanpreet Chahal; Ilgiz A. Salakhov; Charlène Lacourt; Irina I. Semina; Rouslan I. Mousta...; Vitaliy V. Khutor...
• Keywords: Penetration (warfare); Benzalkonium chloride

Crown ethers are cyclic molecules consisting of a ring containing several ether groups. The most common and important members this series 12-crown-4 (12C4), 15-crown-5 (15C5), 18-crown-6 (18C6). These container have the ability to sequester metal ions, their complexes with drugs able traverse cell membranes. This study investigated 12C4, 15C5, 18C6 for increase solubility ocular enhance penetration into cornea. Phase analysis determined crown ethers' riboflavin, drug used therapy keratoconus, these solutions were permeation enhancing properties. Atomic absorption spectroscopy demonstrated solutions' Ca2+ from corneal epithelia, mediated adsorption riboflavin stroma was investigated. Induced opacity studies assessed potential toxicity ethers. enhanced riboflavin's aqueous its in vitro bovine corneas; smaller sized gave greatest enhancement. They shown ions epithelia; doing so loosens cellular membrane tight junctions thus penetration. similar that afforded by benzalkonium chloride less than is produced using polyaminocarboxylic acids. However, vivo experiments performed rats 12C4 did not show any statistically significant permeability enhancement compared enhancer-free formulation.