Thermodynamically stable ionic liquid microemulsions pioneer pathways for topical delivery and peptide application

Tianqi Liu; Ying Liu; Xiaoyu Zhao; Liguo Zhang; Wei Wang; De Bai; Ya Liao; Zhenyuan Wang; Mi Wang; Jiaheng Zhang

doi:10.1016/j.bioactmat.2023.10.002

Thermodynamically stable ionic liquid microemulsions pioneer pathways for topical delivery and peptide application

Bioact Mater. 2023 Nov 1:32:502-513. doi: 10.1016/j.bioactmat.2023.10.002. eCollection 2024 Feb.

Authors

Tianqi Liu^{1

2}, Ying Liu³, Xiaoyu Zhao⁴, Liguo Zhang⁵, Wei Wang⁵, De Bai^{1

2}, Ya Liao⁶, Zhenyuan Wang⁶, Mi Wang^{1

2}, Jiaheng Zhang^{1

2

6}

Affiliations

¹ State Key Laboratory of Advanced Welding and Joining, School of Materials Science and Engineering, Harbin Institute of Technology (Shenzhen), Shenzhen, 518055, China.
² Research Center of Printed Flexible Electronics, School of Materials Science and Engineering, Harbin Institute of Technology, Shenzhen, 518055, China.
³ Department of Chemistry, College of Sciences, Northeastern University, Shenyang, 110819, China.
⁴ CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
⁵ Harbin Voolga Technology Co., Ltd., Harbin, 150070, China.
⁶ Shenzhen Shinehigh Innovation Technology Co., Ltd., Shenzhen, 518055, China.

Abstract

Copper peptides (GHK-Cu) are a powerful hair growth promoter with minimal side effects when compared with minoxidil and finasteride; however, challenges in delivering GHK-Cu topically limits their non-invasive applications. Using theoretical calculations and pseudo-ternary phase diagrams, we designed and constructed a thermodynamically stable ionic liquid (IL)-based microemulsion (IL-M), which integrates the high drug solubility of ILs and high skin permeability of microemulsions, thus improving the local delivery of copper peptides by approximately three-fold while retaining their biological function. Experiments in mice validated the effectiveness of our proposed IL-M system. Furthermore, the exact effects of the IL-M system on the expression of growth factors, such as vascular endothelial growth factor, were revealed, and it was found that microemulsion increased the activation of the Wnt/β-catenin signaling pathway, which includes factors involved in hair growth regulation. Overall, the safe and non-invasive IL microemulsion system developed in this study has great potential for the clinical treatment of hair loss.

Keywords: Bio-based ionic liquids; Copper peptides; Hair regeneration; Microemulsion; Transdermal delivery.