Improving dermal delivery of hydrophilic macromolecules by biocompatible ionic liquid based on choline and malic acid

• Published in: International journal of pharmaceutics Vol. 558; pp. 380 - 387
• Main Authors: Wu, Xiying, Chen, Zhongjian, Li, Yang, Yu, Qin, Lu, Yi, Zhu, Quangang, Li, Ying, An, Duopeng, Qi, Jianping, Wu, Wei
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10-03-2019
• Subjects: Choline; Dermal; Dextran; Ionic liquids; Macromolecules; Malic acid; Dextran; Ionic liquids; Malic acid; Dermal; Choline; Macromolecules
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2019.01.021

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The aim of this work was to develop biocompatible ionic liquids (ILs) for enhancement of dermal delivery of hydrophilic macromolecules. The ILs were prepared from malic acid and choline, which are commonly used as food additives and generally regarded as safe. The choline malate IL (CM-IL) was formed via ionic interactions, which has been validated by Fourier transform infrared spectroscopy and nuclear magnetic resonance. Analysis by differential scanning calorimetry confirmed a melting point of −65.2 °C for CM-IL. In skin penetration study, CM-IL was proved to be able to deliver a model hydrophilic macromolecule dextran into deep skin. The amount of dextran delivered to epidermis and dermis by CM-IL is approximately two folds that of by dextran solution. Enhanced in vivo skin penetration by CM-IL was proved as well. The fluorescence of FITC-dextran could be observed permeating pervasively throughout the skin from 4 h to 24 h, while in the control groups it was mainly concentrated in stratum cornea (SC) and hair follicles. In addition, CM-IL did not shown any irritation to mice skin within 7 days of successive treatment and any toxicity to human epidermal cells (HEK-A) within 24 h. In conclusion, CM-IL could be potentially used as enhancers or vehicles for dermal delivery of hydrophilic macromolecules.