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AAPS PharmSciTech
Nov 11, 2022;23 (8): 296.

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.

Tomohiko Sano, Akie Okada, Kazunori Kawasaki, Takuji Kume, Minoru Fukui, Hiroaki Todo, Kenji Sugibayashi
Author Information
  1. Tomohiko Sano: Faculty of Life & Health Science, Teikyo University of Science, 2-2-1, Senjyu-Sakuragi Adachi-Ku, Tokyo, 121-0045, Japan. sano-tmhk@ntu.ac.jp. ORCID
  2. Akie Okada: Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan.
  3. Kazunori Kawasaki: Biomedical Research Institute, AIST, 1-8-31 Midorigaoka, Ikeda, Osaka, 563-8577, Japan.
  4. Takuji Kume: R&D-Development Research, Kao Corporation, 1334 Minato, Wakayama, 640-8580, Japan.
  5. Minoru Fukui: Research and Innovation Promotion Headquarter, AIST, 1-8-31 Midorigaoka, Ikeda, Osaka, 563-8577, Japan.
  6. Hiroaki Todo: Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan.
  7. Kenji Sugibayashi: Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan.
PMID: 36369392 DOI: 10.1208/s12249-022-02452-0

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 L phase. GET6BG20 and GET6BG60 significantly enhanced the skin permeation of the hydrophilic model drug, antipyrine (ANP) (log K, - 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.

Keywords

L3 phase antipyrine glyceryl ether lamellar repeated distance

References

Bos JD, Meinardi MMHM. The 500 Dalton rule for the skin penetration of chemical compounds and drugs. Exp Dermatol. 2000;9(3):165–9. https://doi.org/10.1034/j.1600-0625.2000.009003165.x . [DOI: 10.1034/j.1600-0625.2000.009003165.x]
Scheuplein RJ, Blank IH. Permeability of the skin. Physiol Rev. 1971;51(4):702–47. [DOI: 10.1152/physrev.1971.51.4.702]
Blank IH. Further observations on factors which influence the water content of the stratum corneum. J Invest Dermatol. 1953;21(4):259–71. https://doi.org/10.1038/jid.1953.100 . [DOI: 10.1038/jid.1953.100]
Muller RH, Mader K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery - a review of the state of the art. Eur J Pharm Biopharm. 2000;50(1):161–77. [DOI: 10.1016/S0939-6411(00)00087-4]
Kogan A, Garti N. Microemulsions as transdermal drug delivery vehicles. Adv Coll Interface Sci. 2006;123–126:369–85. https://doi.org/10.1016/j.cis.2006.05.014 . [DOI: 10.1016/j.cis.2006.05.014]
Schreier H, Bouwstra J. Liposomes and niosomes as topical drug carriers: dermal and transdermal drug delivery. J Control Release. 1994;30(1):1–15. https://doi.org/10.1016/0168-3659(94)90039-6 . [DOI: 10.1016/0168-3659(94)90039-6]
Benson HA. Elastic liposomes for topical and transdermal drug delivery. Methods Mol Biol. 2017;1522:107–17. https://doi.org/10.1007/978-1-4939-6591-5_9 . [DOI: 10.1007/978-1-4939-6591-5_9]
Barauskas J, Johnsson M, Tiberg F. Self-assembled lipid superstructures: beyond vesicles and liposomes. Nano Lett. 2005;5(8):1615–9. https://doi.org/10.1021/nl050678i . [DOI: 10.1021/nl050678i]
Barauskas J, Misiunas A, Gunnarsson T, Tiberg F, Johnsson M. “Sponge” nanoparticle dispersions in aqueous mixtures of diglycerol monooleate, glycerol dioleate, and polysorbate 80. Langmuir : ACS J Surf Coll. 2006;22(14):6328–34. https://doi.org/10.1021/la060295f . [DOI: 10.1021/la060295f]
Engström S, Wadsten-Hindrichsen P, Hernius B. Cubic, sponge, and lamellar phases in the glyceryl monooleyl ether−propylene glycol−water system. Langmuir : ACS J Surf Coll. 2007;23(20):10020–5. https://doi.org/10.1021/la701217b . [DOI: 10.1021/la701217b]
Popescu G, Barauskas J, Nylander T, Tiberg F. Liquid crystalline phases and their dispersions in aqueous mixtures of glycerol monooleate and glyceryl monooleyl ether. Langmuir : ACS J Surf Coll. 2007;23(2):496–503. https://doi.org/10.1021/la062344u . [DOI: 10.1021/la062344u]
Suzuki Y, Tsutsumi H. Emulsifying Characteristics of α-monoalkyl glyceryl ether. J Japan Oil Chem Soc. 1987;36(8):588–93. https://doi.org/10.5650/jos1956.36.588 . [DOI: 10.5650/jos1956.36.588]
Suzuki A, Yamaguchi T, Kawasaki K, Hase T, Tokimitsu I. Enhancing effect of α-monoisostearyl glyceryl ether on the percutaneous penetration of indomethacin through excised rat skin. Biol Pharm Bull. 2001;24(6):698–700. https://doi.org/10.1248/bpb.24.698 . [DOI: 10.1248/bpb.24.698]
Suzuki A, Yamaguchi T, Kawasaki K, Hase T, Tokimitsu I. Alpha-monoisostearyl glyceryl ether enhances percutaneous penetration of indometacin in-vivo. J Pharm Pharmacol. 2002;54(12):1601–7. https://doi.org/10.1211/002235702342 . [DOI: 10.1211/002235702342]
Alfons K, Engstrom S. Drug compatibility with the sponge phases formed in monoolein, water, and propylene glycol or poly(ethylene glycol). J Pharm Sci. 1998;87(12):1527–30. https://doi.org/10.1021/js980209z . [DOI: 10.1021/js980209z]
Uchida T, Yakumaru M, Nishioka K, Higashi Y, Sano T, Todo H, et al. Evaluation of a silicone membrane as an alternative to human skin for determining skin permeation parameters of chemical compounds. Chem Pharm Bull. 2016;64(9):1338–46. https://doi.org/10.1248/cpb.c16-00322 . [DOI: 10.1248/cpb.c16-00322]
Morimoto Y, Hatanaka T, Sugibayashi K, Omiya H. Prediction of skin permeability of drugs: comparison of human and hairless rat skin. J Pharm Pharmacol. 1992;44(8):634–9. https://doi.org/10.1111/j.2042-7158.1992.tb05484.x . [DOI: 10.1111/j.2042-7158.1992.tb05484.x]
Hatanaka T, Inuma M, Sugibayashi K, Morimoto Y. Prediction of skin permeability of drugs: I: comparison with artificial membrane. Chem Pharm Bull. 1990;38(12):3452–9. https://doi.org/10.1248/cpb.38.3452 . [DOI: 10.1248/cpb.38.3452]
Heuser J. Preparing biological samples for stereomicroscopy by the quick-freeze, deep-etch, rotary-replication technique. Methods Cell Biol. 1981;22:97–122. https://doi.org/10.1016/s0091-679x(08)61872-5 . [DOI: 10.1016/s0091-679x(08)61872-5]
Severs NJ. Freeze-fracture electron microscopy. Nat Protoc. 2007;2(3):547–76. https://doi.org/10.1038/nprot.2007.55 . [DOI: 10.1038/nprot.2007.55]
Iikura H, Uchida K, Ogawa-Fuse C, Bito K, Naitou S, Hosokawa M, et al. Effects of temperature and humidity on the skin permeation of hydrophilic and hydrophobic drugs. AAPS PharmSciTech. 2019;20(7):264. https://doi.org/10.1208/s12249-019-1481-1 . [DOI: 10.1208/s12249-019-1481-1]
Wester RC, Christoffel J, Hartway T, Poblete N, Maibach HI, Forsell J. Human cadaver skin viability for in vitro percutaneous absorption: storage and detrimental effects of heat-separation and freezing. Pharm Res. 1998;15(1):82–4. https://doi.org/10.1023/a:1011904921318 . [DOI: 10.1023/a]
Fushimi T, Uchino T, Miyazaki Y, Hatta I, Asano M, Fujino H, et al. Development of phospholipid nanoparticles encapsulating 3-O-cetyl ascorbic acid and tocopherol acetate (TA-Cassome) for improving their skin accumulation. Int J Pharm. 2018;548(1):192–205. https://doi.org/10.1016/j.ijpharm.2018.06.030 . [DOI: 10.1016/j.ijpharm.2018.06.030]
Iliopoulos F, Sil BC, Monjur Al Hossain ASM, Moore DJ, Lucas RA, Lane ME. Topical delivery of niacinamide: Influence of neat solvents. Int J Pharm. 2020;579:119137.   https://doi.org/10.1016/j.ijpharm.2020.119137 .
Hoffmann H, Thunig C, Munkert U, Meyer HW, Richter W. From vesicles to the L3 (sponge) phase in alkyldimethylamine oxide/heptanol systems. Langmuir : ACS J Surf Coll. 1992;8(11):2629–38. https://doi.org/10.1021/la00047a011 . [DOI: 10.1021/la00047a011]
Strey R, Jahn W, Porte G, Bassereau P. Freeze fracture electron microscopy of dilute lamellar and anomalous isotropic (L3) phases. Langmuir : ACS J Surf Coll. 1990;6(11):1635–9. https://doi.org/10.1021/la00101a003 . [DOI: 10.1021/la00101a003]
Imura T, Ohta N, Inoue K, Yagi N, Negishi H, Yanagishita H, et al. Naturally engineered glycolipid biosurfactants leading to distinctive self-assembled structures. Chemistry. 2006;12(9):2434–40. https://doi.org/10.1002/chem.200501199 . [DOI: 10.1002/chem.200501199]
Maldonado A, Ober R, Gulik-Krzywicki T, Urbach W, Langevin D. The sponge phase of a mixed surfactant system. J Colloid Interface Sci. 2007;308(2):485–90. https://doi.org/10.1016/j.jcis.2007.01.012 . [DOI: 10.1016/j.jcis.2007.01.012]
Imura T, Hikosaka Y, Worakitkanchanakul W, Sakai H, Abe M, Konishi M, et al. Aqueous-phase behavior of natural glycolipid biosurfactant mannosylerythritol lipid A: sponge, cubic, and lamellar phases. Langmuir : ACS J Surf Coll. 2007;23(4):1659–63. https://doi.org/10.1021/la0620814 . [DOI: 10.1021/la0620814]
Fujii MY, Asakawa Y, Fukami T. Potential application of novel liquid crystal nanoparticles of isostearyl glyceryl ether for transdermal delivery of 4-biphenyl acetic acid. Int J Pharm. 2020;575:118935. https://doi.org/10.1016/j.ijpharm.2019.118935 . [DOI: 10.1016/j.ijpharm.2019.118935]
Uchino T, Kato S, Hatta I, Miyazaki Y, Suzuki T, Sasaki K, et al. Study on the drug permeation mechanism from flurbiprofen-loaded glyceryl monooleyl ether-based lyotropic liquid crystalline nanoparticles across the skin: Synchrotron X-ray diffraction and confocal laser scanning microscopy study. Int J Pharm. 2019;555:259–69. https://doi.org/10.1016/j.ijpharm.2018.11.031 . [DOI: 10.1016/j.ijpharm.2018.11.031]
Hussain A, Singh S, Sharma D, Webster TJ, Shafaat K, Faruk A. Elastic liposomes as novel carriers: recent advances in drug delivery. Int J Nanomed. 2017;12:5087–108. https://doi.org/10.2147/ijn.S138267 . [DOI: 10.2147/ijn.S138267]
El Maghraby GM, Barry BW, Williams AC. Liposomes and skin: From drug delivery to model membranes. Eur J Pharm Sci. 2008;34(4–5):203–22. https://doi.org/10.1016/j.ejps.2008.05.002 . [DOI: 10.1016/j.ejps.2008.05.002]
Benson HA. Transfersomes for transdermal drug delivery. Expert Opin Drug Deliv. 2006;3(6):727–37. https://doi.org/10.1517/17425247.3.6.727 . [DOI: 10.1517/17425247.3.6.727]
Opatha SAT, Titapiwatanakun V, Chutoprapat R. Transfersomes: a promising nanoencapsulation technique for transdermal drug delivery. Pharmaceutics. 2020;12(9). https://doi.org/10.3390/pharmaceutics12090855 .
Jiang T, Wang T, Li T, Ma Y, Shen S, He B, et al. Enhanced transdermal drug delivery by transfersome-embedded oligopeptide hydrogel for topical chemotherapy of melanoma. ACS Nano. 2018;12(10):9693–701. https://doi.org/10.1021/acsnano.8b03800 . [DOI: 10.1021/acsnano.8b03800]

MeSH Term

Administration, Cutaneous
Glyceryl Ethers
Lipids
Permeability
Pharmaceutical Preparations
Skin
Surface-Active Agents
Water

Chemicals

Glyceryl Ethers
Lipids
Pharmaceutical Preparations
Surface-Active Agents
Water
Journal Article

Word Cloud

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