Comparison of Ionic Liquids and Chemical Permeation Enhancers for Transdermal Drug Delivery

Abstract

Transdermal delivery offers a patient-friendly method of drug administration. An ideal formulation for transdermal drug delivery should have high potency to enhance skin permeation and low tendency to induce skin irritation. Ionic liquids (ILs) and deep eutectic solvents (DESs) have recently been proposed to serve as an excellent platform to enable transdermal delivery of various therapeutics including proteins and siRNA. In spite of their success, general safety-efficacy behavior of ILs/DESs is not reported. Using safety and efficacy as two design criteria, a Fourier transform infrared (FTIR) spectroscopy study is conducted to compare the performance of 31 ammonium-based ILs/DESs and 44 conventional chemical permeation enhancer (CPE) molecules. FTIR analysis of skin stratum corneum exposed to ILs/DESs and CPEs is performed to extract features indicative of their safety and efficacy. ILs/DESs, as a class, outperformed conventional CPEs in terms of both potency and safety. Analysis of ILs/DESs and CPEs based on Hansen solubility parameters indicates that ILs/DESs possess solubility parameters close to those of skin, which may explain their superiority over CPEs. These studies support ILs/ DESs as promising materials for novel drug delivery systems.

Grape Pomace for Topical Application: Green NaDES Sustainable Extraction, Skin Permeation Studies, Antioxidant and Anti-Inflammatory Activities Characterization in 3D Human Keratinocytes

“…In the present work, polyphenols from red grape pomace were extracted with the greener alternative of natural deep eutectic solvents (NaDESs), both as extracting agents and polyphenols carriers, incorporating NaDESs into bioactive formulations. NaDESs have recently been proposed as an excellent platform to enable transdermal delivery of various therapeutics, including proteins and siRNA, with a higher capacity for skin permeation and lower tendency to induce skin irritation compared to conventional chemical permeation enhancer (CPE) molecules [20].…”

Enhancing the Solubility and Transdermal Delivery of Drugs Using Ionic Liquid‐In‐Oil Microemulsions

“…[34] The MAC with different compositions may exhibit different interion interactions. 1 H nuclear Overhauser effect spectroscopy (NOESY) of 1:1 MAC (1:1 ratio between L-(-)-carnitine and MA) indicates that the main interaction is between the proton (terminal methyl) attached to the sp 3 carbon and the methyl group connected to the nitrogen atom of L-(-)-carnitine (Figure S4, Supporting Information). The interspace interaction between the hydroxyl proton in L-(-)-carnitine and its internal protons is consistent with the theoretical calculations (Figure 1b,c).…”

“…Compared with conventional drug delivery systems, such as oral administration and injection, transdermal drug delivery has many advantages because it avoids first‐pass liver clearance, improves drug dependence, and reduces the side effects of drugs. [ 1–3 ] However, transdermal delivery is often difficult due to the insolubility or poor solubility of drugs in water. [ 4,5 ] As it is well known, many insoluble drugs have never entered clinical trials owing to their poor solubility and delivery difficulty.…”

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

“…Thus, the CPE action of hydrophilic ILs (e.g., 1-ethyl-3-methylimidazolium-based) has been mostly ascribed to their role as polar enhancers able to (i) increase solubility and partition of hydrophilic drugs, and/or (ii) fluidize the SC by disrupting the tight packing of both proteins and lipids (at the headgroups level— Figure 8 ). In turn, hydrophobic ILs, many of which are SAILs (e.g., CPC, 1-dodecyl-3-methylimidazolium-based ILs), may exert their skin permeation action by (i) increasing solubility and partition of hydrophobic drugs, (ii) inserting into the SC lipid bilayers, causing a disruption of the ordered packing of the phospholipid bilayers or even phase separation or induction of lamellar phases ( Figure 8 ), and/or (iii) extracting SC lipids [ 124 , 128 , 129 , 130 , 131 ]. Interestingly, SC lipid extraction followed by replacement of the extracted lipids with the IL and water has been recently advanced as the mechanism by which CAGE enhances the skin permeation of macromolecules like dextran [ 132 ].…”