Protic ionic liquid-driven vesicles: structural and physicochemical insights into a potential nanocarrier for gastrointestinal drug delivery

Abstract

The protic ionic liquid-surfactant imim-AOT (1-methylimidazolium 1,4-bis-2-ethylhexylsulfosuccinate) spontaneously self-assembles into unilamellar vesicles in aqueous solution at room temperature, without the need for external energy input. The protic character of the imim⁺ cation appears to play a key role in the vesicle-forming capability of imim-AOT. These vesicular aggregates exhibit an average diameter of 122-132 nm, a low polydispersity index (~0.25), and a strongly negative ζ-potential (-55 ± 5 mV), indicating pronounced electrostatic repulsion and excellent colloidal stability. The vesicles remain stable over extended periods (weeks) and across a broad pH range (2.4-8.1), including highly acidic conditions that mimic the gastric environment. In vitro cytotoxicity studies using Vero cells evaluated through MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and neutral red uptake (NRU) assays revealed low cytotoxicity, with cell viability maintained at or above 80% for imim-AOT concentrations ≤ 6x10-5 M. These findings highlight imim-AOT vesicles as candidates for potential application in the oral delivery of bioactive compounds.