Biocompatible Ionic Liquid Enhances Transdermal Antigen Peptide Delivery and Preventive Vaccination Effect

被引:42
|
作者
Tahara, Yoshiro [3 ]
Morita, Kaho [3 ]
Wakabayashi, Rie [2 ,3 ]
Kamiya, Noriho [1 ,2 ]
Goto, Masahiro [1 ,2 ]
机构
[1] Kyushu Univ, Dept Appl Chem, Grad Sch Engn, Ctr Future Chem, Fukuoka 8190395, Japan
[2] Kyushu Univ, Ctr Adv Transdermal Drug Delivery Syst Ctr, Fukuoka 8190395, Japan
[3] Kyushu Univ, Grad Sch Engn, Dept Appl Chem, Fukuoka 8190395, Japan
基金
日本学术振兴会;
关键词
ionic liquid; transdermal delivery; peptide; biocompatible; vaccine; IN-OIL NANODISPERSIONS; SKIN PERMEATION; ACID; CHOLINE; IMMUNIZATION; IMMUNOTHERAPY; LIDOCAINE; CARRIER; ESTERS; DRUGS;
D O I
10.1021/acs.molpharmaceut.0c00598
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:3845 / 3856
页数:12
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