Synergistic aggregation of the ibuprofenate anion and a a double-strand imidazolium cation into vesicles for drug delivery: a simulation study

The drug delivery process is a challenging topic that interfaces with the pharmaceutical and medical sciences. Herein the capability of a benign double-strand long-chain ionic liquid based-lipid (1,3-dimethyl-4,5-pentadecyl-imidazolium iodide ([2(Me)2(C-15)im]I) in ibuprofen(Ibu) drug delivery is reported via molecular dynamics (MD) simulation for the first time. Merging the [2(Me)2(C-15)im](+) cation and the ibuprofenate ([Ibu](-)) anion makes a novel ion-pair that can aggregate in a fascinating shape in aqueous media. Such aggregation benefits synergy and leads to the formation of stable cylindrical and spherical vesicles at higher and lower concentrations, respectively. These vesicles indeed involve the [Ibu](-) as a building block of the drug carrier. The net surface charge of spherical vesicles provide the stability of their suspension; the monovalent (NaCl) solution enhances the stability of suspension due to surface charge enhancement. The coagulation of the suspended vesicles found in divalent (CaCl2) salts solution occurs through the complexation with head groups. The radial distribution function (RDF) reveals the solid-like character of the vesicle wall, evidencing the synergistic aggregation. The extended stability of spherical vesicles (involving the drug carrier ion-pair [2(Me)2(C-15)im][Ibu]) in the monovalent salt solution is remarkably resembling the human body extracellular fluid and plasma. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

A novel ionic liquid-based lipid has been studied for drug delivery, showing the formation of stable vesicles as drug carriers in aqueous media through the formation of ion pairs. The addition of monovalent salts enhances the stability of the vesicles, while divalent salts lead to coagulation through complexation with head groups. The solid-like character of the vesicle wall is evidenced by the radial distribution function, indicating synergistic aggregation.