Available online 1 September 2022, 106290

Ionic liquid (IL) were obtained by mixing of etodolac(ETD) and proline ethyl ester in a molar ratio of 1: 2.

ETD/ProOEt IL exhibited a significant increase in ETD solubility in the simulated nasal fluid.

The nasal retention and brain delivery of ETD by nasal administration of ETD/ProOEt IL were increased by 3-fold or 7-fold compared to the ETD solution, respectively.

PGE₂ production in the brain of the inflammatory model mice was significantly suppressed by approximately 40% at 60 min after the intranasal administration of IL solution compared to that of the untreated group.

The purpose of this study was to enhance the delivery of Etodolac (ETD) to the brain through intranasal administration using an ionic liquid (IL) consisting of ETD and proline ethyl ester. The IL of ETD was prepared by mixing ETD with proline ethyl ester as a counterion in a molar ratio of 1:2.The formation of the IL was confirmed by differential scanning calorimetry (DSC), infrared spectroscopy (IR) and proton nuclear magnetic resonance (1H-NMR).The solubility of ETD in simulated nasal fluids was improved by approximately 200-fold due to the formation of IL. The intranasal administration of ETD-containing IL, which is viscous, increased the nose-to-brain delivery by approximately 7-fold 30 min after an administration of the ETD solution alone. The enhancement of ETD delivery to the brain from the nose was attributed to the enhanced retention of ETD in the nasal mucosal surface due to the viscosity of IL. The induction of prostaglandin E2 in the brain inflammation that was induced by lipopolysaccharides was significantly suppressed by up to 40% in the IL-treated group compared with the drug-untreated group. Therefore, ETD-containing IL were suggested to be useful in designing intranasal formulations for the nasal delivery of ETDs to the brain.

Ionic liquids

nose-to-brain delivery

etodolac

brain inflammation

prostaglandin E2

© 2022 The Authors. Published by Elsevier B.V.