TY - JOUR
T1 - Choline and amino acid based biocompatible ionic liquid mediated transdermal delivery of the sparingly soluble drug acyclovir
AU - Islam, Md Rafiqul
AU - Chowdhury, Md Raihan
AU - Wakabayashi, Rie
AU - Tahara, Yoshiro
AU - Kamiya, Noriho
AU - Moniruzzaman, Muhammad
AU - Goto, Masahiro
N1 - Funding Information:
This study was supported by the Japan Society for the Promotion of Science (JSPS) ( KAKENHI No. JP20K20440 ). M. R. Islam thanks the Government of Japan (MEXT) for providing the scholarship to carry out higher study and research at Kyushu University. We thank Dr. M. Watanabe and Prof. Y. Hirano for providing NMR and elemental analysis facilities, respectively. We also thank Tim Cooper, PhD, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/5/30
Y1 - 2020/5/30
N2 - Transdermal delivery of drugs is more challenging for drugs that are insoluble or sparingly soluble in water and most organic solvents. To overcome this problem, ionic liquid (IL)-mediated ternary systems have been suggested as potential drug carriers. Here, we report potent ternary (IL–EtOH–IPM) systems consisting of biocompatible ILs, ethanol (EtOH), and isopropyl myristate (IPM) that can dissolve a significant amount of the sparingly soluble drug acyclovir (ACV). The ternary systems were optically transparent and thermodynamically stable with a wide range of IL pertinence. An in vitro drug permeation study showed that the ILs in the ternary systems dramatically enhanced ACV permeation into and across the skin. Fourier Transform Infrared spectroscopy of the stratum corneum (sc) after treatment with ternary systems showed that the skin barrier function was reduced by disturbance of the regularly ordered arrangement of corneocytes and modification of the surface properties of the sc during permeation. Histological analysis, and skin irritation studies using a reconstructed human epidermis model showed the safety profile of the ternary system, and there were no significant changes in the structures of the sc, epidermis, and dermis. Therefore, ternary systems containing biocompatible ILs are promising for transdermal delivery of insoluble or sparingly soluble drugs.
AB - Transdermal delivery of drugs is more challenging for drugs that are insoluble or sparingly soluble in water and most organic solvents. To overcome this problem, ionic liquid (IL)-mediated ternary systems have been suggested as potential drug carriers. Here, we report potent ternary (IL–EtOH–IPM) systems consisting of biocompatible ILs, ethanol (EtOH), and isopropyl myristate (IPM) that can dissolve a significant amount of the sparingly soluble drug acyclovir (ACV). The ternary systems were optically transparent and thermodynamically stable with a wide range of IL pertinence. An in vitro drug permeation study showed that the ILs in the ternary systems dramatically enhanced ACV permeation into and across the skin. Fourier Transform Infrared spectroscopy of the stratum corneum (sc) after treatment with ternary systems showed that the skin barrier function was reduced by disturbance of the regularly ordered arrangement of corneocytes and modification of the surface properties of the sc during permeation. Histological analysis, and skin irritation studies using a reconstructed human epidermis model showed the safety profile of the ternary system, and there were no significant changes in the structures of the sc, epidermis, and dermis. Therefore, ternary systems containing biocompatible ILs are promising for transdermal delivery of insoluble or sparingly soluble drugs.
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U2 - 10.1016/j.ijpharm.2020.119335
DO - 10.1016/j.ijpharm.2020.119335
M3 - Article
C2 - 32311469
AN - SCOPUS:85083436723
VL - 582
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
M1 - 119335
ER -