# Ionic Liquids as Antibacterial and Drug Delivery Agents: How Cationic Amphiphilic Structure Controls Morphology Changes in Lipid Bilayers and Penetration Mechanism

## TL;DR

This study explores how the structure of ionic liquids affects their interaction with cell membranes, revealing different mechanisms for drug delivery and antibacterial action.

## Contribution

The paper introduces a detailed analysis of how cationic amphiphilic structure influences lipid bilayer morphology and penetration mechanisms.

## Key findings

- Cations with a 16-carbon chain can partially remove lipid molecules from bilayers in concentrated solutions.
- Cations with two long tails increase bilayer thickness by penetrating the hydrophobic core.
- Two distinct drug delivery mechanisms are proposed based on water solubility and clustering tendency.

## Abstract

Ionic liquid-based
technologies are promising both as antibacterial
agents and in drug delivery, as they can improve drug solubility and
capacity to bypass lipid bilayers while also taking advantage of ionic
liquids’ physical properties, such as negligible vapor pressure
and stability. In both applications, it is imperative to understand
how the molecular structure of the ionic liquid determines its interaction
with cellular membranes. In this work, molecular dynamics simulations
with coarse-grained models were applied to study the penetration of
eight ionic liquids based on the 1,3-dialkyl-imidazolium cation with
different alkyl group sizes into DPPC bilayers from both dilute and
concentrated aqueous solutions. Potential of mean force calculations
were performed to evaluate the thermodynamics of cation penetration,
and graph theory was used to characterize their nonhomogeneous distributions
inside the bilayers. Distinct effects were noticed over the bilayer
morphology: Cations with a single small or medium alkyl tail do not
induce significant changes over the bilayer structure, while cations
with a 16-carbon-atom chain are water-insoluble and, in concentrated
solutions, are capable of partially removing lipid molecules. Incorporated
cations with two medium-sized tails remain close to the water interface,
reducing the interaction between lipids and decreasing the bilayer
thickness, while cations with two long tails penetrate into the hydrophobic
center of the bilayer and increase its thickness instead. As a consequence
of the different interactions, two distinct mechanisms have been proposed
for the drug delivery action of ionic liquids, depending on their
water solubility and clustering tendency.