Ionic liquids and their potential use in development and improvement of drug delivery systems: evidence of their tendency to promote drug accumulation in the brain

Abstract

Ionic liquids (ILs) are considered salt in liquid state, which is composed of organic cations and anions with low melting points (<100 °C). ILs have become a major scientific area with an extensive range of applications including chemistry, electrochemistry, and pharmaceutics. ILs have received great research interest in the pharmaceutical field as solvents, anti-solvents, co-solvents, and reagents in synthesis and formulation. While therapeutic ILs have been investigated for oral and trans-dermal drug delivery systems showing promising compatibility with a wide range of therapeutics, enhanced drug permeation through the skin, and cell membrane solvation to open channels to facilitate molecular passage, their potential to cross the challenging blood-brain barrier (BBB) remains an unanswered question. IL-based therapies could potentially be a game changer for improving drug delivery to cellular targets both at and across the BBB. In this review, we discuss (1) the tunable physicochemical properties of ILs; (2) the vast and various applications of ILs in the development and improvement of drug delivery systems; and (3) ILs as a potential approach for increasing drug accumulation in the brain tissue.

Keywords: Ionic liquids; blood-cerebrospinal fluid barrier; blood–brain barrier; brain drug delivery; drug delivery systems.

Figure 1.

BBB – The blood vessels that vascularize the CNS regulate the movement of therapeutics between the blood and the brain, preventing any solutes or pathogens in the circulating blood from entering the brain.

Figure 2.

The brain endothelial tight junction complex.

Figure 3.

Invasive and non-invasive techniques for brain drug delivery.

Figure 4.

Topical and transdermal ILs penetrate the stratum corneum: (1) hydrate the stratum corneum, (2) interact with the lipids, thus disrupting the lipid packing (3) pass through the tight junctions between skin cells for deeper penetration, thus improving drug uptake and intracellular distribution