Department of Applied Chemistry, Graduate School of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
Center for Advanced Transdermal Drug Delivery System Center, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
Mol Pharm. 2020 Oct 5;17(10):3845-3856. doi: 10.1021/acs.molpharmaceut.0c00598. Epub 2020 Sep 21.
Ionic liquids (ILs) attract significant attention as novel solvents for drug delivery systems because of their ability to solubilize poorly soluble drugs and tune the physiological properties of active pharmaceutical ingredients. For the next generation of IL-based drug delivery systems, biocompatibility is a high priority. In the current study, choline-fatty acids ([Cho][FA]) were used as a biocompatible IL to mediate the dissolution of a water-soluble antigen peptide in an oil-based skin penetration enhancer. Among the candidate fatty acids (C8, C10, C12, C14, C16, C18:0, and C18:1), C18:1 was selected because of its low cytotoxicity and mediation of skin permeability for an antigen peptide. Using IL[Cho][C18:1] and an oil-based penetration enhancer, the flux of transdermal delivery of the peptide increased 28-fold compared with delivery using an aqueous vehicle. Furthermore, the IL-mediated transcutaneous vaccination succeeded in suppressing tumor growth in vivo compared to injection. The skin irritation produced by this formulation was tested using an in vitro 3D constructed skin tissue model and an in vivo histological study, which concluded that the formulation did not cause skin irritation. The results suggest that biocompatible IL-mediated dissolution in an oil-based skin penetration enhancer is a promising strategy for transdermal drug delivery.
离子液体（ILs）因其能够溶解难溶性药物和调节活性药物成分的生理特性而引起了人们对药物传递系统的极大关注。对于下一代基于 IL 的药物传递系统，生物相容性是一个高度优先考虑的问题。在当前的研究中，胆碱脂肪酸（[Cho][FA]）被用作生物相容的 IL，以介导水溶性抗原肽在油基皮肤渗透增强剂中的溶解。在候选脂肪酸（C8、C10、C12、C14、C16、C18:0 和 C18:1）中，由于其低细胞毒性和介导抗原肽的皮肤渗透性，选择了 C18:1。使用 IL[Cho][C18:1]和油基渗透增强剂，与使用水性载体相比，肽的透皮传递通量增加了 28 倍。此外，与注射相比，IL 介导的经皮接种成功抑制了体内肿瘤生长。使用体外 3D 构建的皮肤组织模型和体内组织学研究测试了该制剂引起的皮肤刺激，结果表明该制剂不会引起皮肤刺激。结果表明，生物相容的 IL 介导的油基皮肤渗透增强剂中的溶解是经皮药物传递的一种很有前途的策略。
