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Self-Assembled Structure of α-Isostearyl Glyceryl Ether Affects Skin Permeability—a Lamellar with 70-nm Spaces and L3 Phase Enhanced the Transdermal Delivery of a Hydrophilic Model Drug

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Abstract

Self-assembled surfactant structures, such as liquid crystals, have the potential to enhance transdermal drug delivery. In the present study, the pseudo-ternary system of GET (composed of α-Isostearyl glyceryl ether (GEIS) and polysorbate 60)/1,3 butanediol (BG)/water) was shown to exhibit a complex phase diagram. Small- and wide-angle X-ray scattering (SWAXS) and freeze-fracture transmission electron microscopy (FF-TEM) revealed that GET6BG60 (6%GET/60%BG/34%Water) formed a lamellar phase with a repeated distance of approximately 72 nm. Such a long-repeated distance of the lamellar phase was unique in the surfactant system. Moreover, the various structures, such as multilamellar vesicles and branched-like layers, were observed, which suggested that they might be deformable. On the other hand, only core–shell particles were observed in GET6BG20, the core of which was an L3 phase. GET6BG20 and GET6BG60 significantly enhanced the skin permeation of the hydrophilic model drug, antipyrine (ANP) (log Ko/w, − 1.51). However, their permeation profiles were distinct. Liquid chromatography-tandem mass spectrometry revealed that epidermal accumulation of GEIS was significantly higher with GET6BG60 than GET6BG20 after 1.5 h of permeation, which might be attributed to differences in their deformable properties. Furthermore, GEIS was reported to affect intercellular lipids. Accumulated GEIS in the epidermis may have interacted with intercellular lipids and enhanced the transdermal delivery of ANP. The difference in the permeation profiles of ANP may be attributed to the penetration process of GEIS in the epidermis. This study suggests that GET6BG20 and GET6BG60 are unique carriers to enhance the permeation of hydrophilic drugs, such as ANP.

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Acknowledgements

The authors thank Dr. Takeyuki Uchida (TIA EM-facility, AIST) for electron microscopy.

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Authors and Affiliations

  1. Faculty of Life & Health Science, Teikyo University of Science, 2-2-1, Senjyu-Sakuragi Adachi-Ku, Tokyo, 121-0045, Japan

    Tomohiko Sano

  2. Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan

    Akie Okada, Hiroaki Todo & Kenji Sugibayashi

  3. Biomedical Research Institute, AIST, 1-8-31 Midorigaoka, Ikeda, Osaka, 563-8577, Japan

    Kazunori Kawasaki

  4. R&D–Development Research, Kao Corporation, 1334 Minato, Wakayama, 640-8580, Japan

    Takuji Kume

  5. Research and Innovation Promotion Headquarter, AIST, 1-8-31 Midorigaoka, Ikeda, Osaka, 563-8577, Japan

    Minoru Fukui

  6. Faculty of Pharmaceutical Sciences, Josai International University, 1 Gumyu Togane, Chiba, 283–8555, Japan

    Kenji Sugibayashi

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  1. Tomohiko Sano
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Contributions

Tomohiko Sano, Hiroaki Todo, and Kazunori Kawasaki substantially contributed to the study conceptualization.

Tomohiko Sano, Akie Okada, and Takuji Kume significantly contributed to data analysis and interpretation.

Tomohiko Sano, Hiroaki Todo, and Kazunori Kawasaki substantially contributed to the manuscript drafting.

Minoru Fukui supported and coordinated the conduct of this study.

Kenji Sugibayashi advised the interpretation of the results and supervised the study.

All authors reviewed the manuscript draft and revised it critically on intellectual content.

All authors approved the final version of the manuscript to be published.

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Correspondence to Tomohiko Sano.

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Sano, T., Okada, A., Kawasaki, K. et al. Self-Assembled Structure of α-Isostearyl Glyceryl Ether Affects Skin Permeability—a Lamellar with 70-nm Spaces and L3 Phase Enhanced the Transdermal Delivery of a Hydrophilic Model Drug. AAPS PharmSciTech 23, 296 (2022). https://doi.org/10.1208/s12249-022-02452-0

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