Non-invasive Transdermal Delivery of Human Insulin Using Ionic Liquids: In vitro Studies

Abstract

In this research project, synthesis and characterization of ionic liquids and their subsequent utilization as facilitators of transdermal delivery of human insulin was pursued. Choline geranate and choline oleate ionic liquids (and their deep eutectic solvents) were produced and characterized by nuclear magnetic resonance ( 1 H NMR), water content, oxidative stability, cytotoxicity and genotoxicity assays, and ability to promote transdermal protein permeation. The results gathered clearly suggest that all ionic liquids were able to promote/facilitate transdermal permeation of insulin, although to various extents. In particular, choline geranate 1:2 combined with its virtually nil cytoand geno-toxicity was chosen to be incorporated in a biopolymeric formulation making it a suitable facilitator aiming at transdermal delivery of insulin.

Revisiting the Physicochemical Properties and Applications of Deep Eutectic Solvents

“…Nonetheless, the absorption promoter or permeation enhancers should be non-toxic, biocompatible, drug compatible, free from adverse pharmacological activity, and cheap [106,109]. In this regard, DESs and ILs have been evaluated [109][110][111][112]. Ionic liquids (ILs) with low vapor pressure and various promising physicochemical properties have also been used as an alternative solvent to organic (volatile) solvents [113,114].…”

The Emerging Role of Ionic Liquid-Based Approaches for Enhanced Skin Permeation of Bioactive Molecules: A Snapshot of the Past Couple of Years

“…Favorable insulin permeation data were recently reported by Mitragotri and co-workers when using CAGE or taurine/carnitine ILs as, respectively, part of a biodegradable polymeric patch for transmucosal delivery [ 164 ], or percutaneous permeation enhancer [ 140 ]. Balcão and co-workers have also investigated the adequacy of CAGE and choline oleate ILs, prepared in a 1:2 cation/anion ratio, for potential use in transdermal delivery of insulin [ 165 ]. The ILs were evaluated regarding cytotoxicity, genotoxicity, oxidative stability, and ability to enhance insulin percutaneous permeation.…”

“…The ILs were evaluated regarding cytotoxicity, genotoxicity, oxidative stability, and ability to enhance insulin percutaneous permeation. CAGE presented the best profile, and was next incorporated in an optimized biopolymer formulation, affording a transdermal patch that efficiently promoted transdermal delivery of human insulin in a pig ear skin ex vivo model [ 165 ].…”

Transdermal permeation of curcumin promoted by choline geranate ionic liquid: Potential for the treatment of skin diseases

“…ILs and their DESs are able to transiently disrupt the skin barrier function by modifying the regular arrangement of the corneocytes of the stratum corneum ( Islam et al, 2020 , Boscariol et al, 2021 ). Choline and geranic acid ionic liquid (CAGE-IL) has been successfully used by our research group to increase skin permeation of several substances, such as insulin ( Jorge et al, 2020 ), phage particles ( Campos et al, 2020 , Silva et al, 2021 ) and curcumin ( Boscariol et al, 2021 ), and also by other research groups ( Banerjee et al, 2017 ).…”