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

• Published in: Advanced functional materials Vol. 31; no. 34
• Main Authors: Lu, Beibei, Bo, Yiyang, Yi, Mingjie, Wang, Zhenyuan, Zhang, Jichuan, Zhu, Zhenye, Zhao, Yanli, Zhang, Jiaheng
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc 01-08-2021
• Subjects: Carnitine; Density functional theory; drug solubility; Hydrogen bonds; Insulin; ionic liquid; Ionic liquids; Ions; Materials science; microemulsion; Microemulsions; Penetration; Proteins; Solubility; transdermal drug delivery; Van der Waals forces
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.202102794

The development of hydrophobic drug and protein delivery carriers remains a challenge. To synthesize L‐(‐)‐carnitine‐based ionic liquid (IL), this study applies the density functional theory to investigate the hydrogen bonds and van der Waals force that govern L‐(‐)‐carnitine‐based IL formation. An ionic liquid‐in‐oil microemulsion (IL/O ME) is then developed to facilitate the transdermal delivery of proteins and increase the solubility of drugs. IL/O ME is prepared using isopropyl myristate (IPM), Tween 80/Span 20, and L‐(‐)‐carnitine‐based IL. The skin permeation studies conducted using mouse skin show that the insulin permeation percentage of the developed IL/O ME is 3.55 folds higher than that of phosphate‐buffered saline and 2.91 folds better than that of a hydrophilic L‐(‐)‐carnitine‐based IL. In addition, the solubility of two drug molecules, that is, rosiglitazone and bezafibrate, in IL/O ME is at least 49.28 folds higher than their solubility in water or IPM. Therefore, IL/O ME can significantly improve the solubility of drugs and increase the permeability of proteins (e.g., insulin), thus demonstrating a promising potential as a delivery carrier.
An ionic liquid‐in‐oil microemulsion system based on L‐(‐)‐carnitine is developed as a versatile drug carrier. Detailed studies indicate that the system can significantly enhance transdermal delivery of insulin and increase the solubility of drugs.