Ionic Liquids as Potential and Synergistic Permeation Enhancers for Transdermal Drug Delivery

Abstract

Transdermal drug delivery systems (TDDS) show clear advantages over conventional routes of drug administration. Nonetheless, there are limitations to current TDDS which warrant further research to improve current TDD platforms. Spurred by the synthesis of novel biodegradable ionic liquids (ILs) and favorable cytotoxicity studies, ILs were shown to be a possible solution to overcome these challenges. Their favorable application in overcoming challenges ranging from synthesis, manufacture, and even therapeutic benefits were documented. In this review, said ILs are highlighted and their role in TDDS is reviewed in terms of (a) ILs as permeation enhancers (single agents or combined), (b) ILs in drug modification, and (c) ILs as active pharmaceutical ingredients. Furthermore, future combination of ILs with other chemical permeation enhancers (CPEs) is proposed and discussed.

Ionic Liquid-In-Oil Microemulsions Prepared with Biocompatible Choline Carboxylic Acids for Improving the Transdermal Delivery of a Sparingly Soluble Drug

“…Despite having various advantages, the use of ILs is limited because of their high toxicity and low biocompatibility and degradability [17]. In fact, most of the ILs used in previous studies, including imidazolium, pyridinium, and quinolinium cations and high strength inorganic acid anion-based ILs cannot be used in clinical applications because of their high toxicity and low biocompatibility [18,19].…”

“Clicking” an Ionic Liquid to a Potent Antimicrobial Peptide: On the Route towards Improved Stability

“…ILs showing broad-spectrum activity against both Gram-negative and Gram-positive bacteria and antibiofilm activity have been reported [ 9 ]; as such, ILs are emerging as appealing alternatives to counteract antimicrobial resistance, while the world is running out of effective antibiotics, especially against Gram-negative bacteria. Moreover, many ILs have gained attention as dermal permeation enhancers [ 10 ], making them particularly attractive for topical applications. ILs presenting both antimicrobial activity and dermal permeation enhancement can be quite helpful to treat infected skin lesions, as recently demonstrated in an in vivo biofilm-infected wound assay, where an IL was able to kill 95% of the bacteria [ 11 ].…”

Cinnamic Acid Conjugates in the Rescuing and Repurposing of Classical Antimalarial Drugs

“…As ionic liquids result from the combination of an acid with an organic base, the mixing of an acidic drug with a basic one is likely to deliver dual-action API-IL based formulations, such as the lidocaine-ibuprofen IL reported by Park and Prausnitz [98], amongst other synergistic IL-based formulations for transdermal delivery, as recently reviewed by Pillay and co-workers [99]. Hence, by virtue of their diverse biological roles and of their acidic nature, CA may offer multiple options for the design of novel API-IL upon their ionic pairing with basic API for different kinds of therapeutic indications.…”