TY - JOUR
T1 - Biocompatible ionic liquid enhances transdermal antigen peptide delivery and preventive vaccination effect
AU - Goto, Masahiro
AU - Tahara, Yoshiro
AU - Morita, Kaho
AU - Wakabayashi, Rie
AU - Goto, Masahiro
N1 - Funding Information:
The authors would like to thank Professors Takeshi Mori and Yoshiki Katayama for allowing us to use their animal experimentation facilities. This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI nos. JP16H06369 and JP20K20440. We thank Conn Hastings, PhD, from the Edanz Group ( www.edanzediting.com/ac ) for editing a draft of this manuscript.
Publisher Copyright:
© 2020 American Chemical Society.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/10/5
Y1 - 2020/10/5
N2 - 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 ILmediated 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.
AB - 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 ILmediated 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.
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U2 - 10.1021/acs.molpharmaceut.0c00598
DO - 10.1021/acs.molpharmaceut.0c00598
M3 - Article
C2 - 32902989
AN - SCOPUS:85092681922
VL - 17
SP - 3845
EP - 3856
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
SN - 1543-8384
IS - 10
ER -