Evaluation of in vitro transdermal permeation, mass spectrometric imaging, and in vivo analgesic effects of pregabalin using a pluronic lecithin organogel formulation in mice

In clinical practice, pregabalin is orally administered for neuropathic pain, but causes severe central nervous system side effects, such as dizziness, which results in dose limitation or discontinuation. To reduce the central side effects of pregabalin, we developed four pregabalin preparations for...

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Main Authors: Michiru Nagao, Masataka Tajima, Erika Sugiyama, Ryosuke Shinouchi, Keita Shibata, Masayuki Yoshikawa, Takushi Yamamoto, Vilasinee Hirunpanich Sato, Koji Nobe, Hitoshi Sato
Other Authors: Shimadzu Corporation
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Published: 2022
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Online Access:https://repository.li.mahidol.ac.th/handle/123456789/75192
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spelling th-mahidol.751922022-08-04T11:47:26Z Evaluation of in vitro transdermal permeation, mass spectrometric imaging, and in vivo analgesic effects of pregabalin using a pluronic lecithin organogel formulation in mice Michiru Nagao Masataka Tajima Erika Sugiyama Ryosuke Shinouchi Keita Shibata Masayuki Yoshikawa Takushi Yamamoto Vilasinee Hirunpanich Sato Koji Nobe Hitoshi Sato Shimadzu Corporation Showa University Mahidol University Neuroscience Pharmacology, Toxicology and Pharmaceutics In clinical practice, pregabalin is orally administered for neuropathic pain, but causes severe central nervous system side effects, such as dizziness, which results in dose limitation or discontinuation. To reduce the central side effects of pregabalin, we developed four pregabalin preparations for transdermal application: 0.4% aqueous solution, pluronic lecithin organogel (PLO gel), hydrophilic cream, and lipophilic cream. Transdermal permeabilities of pregabalin among the four formulations were compared in vitro using hairless mouse skin. The longitudinal distribution of pregabalin within the skin was analyzed using mass spectrometric (MS) imaging. Furthermore, the in vivo analgesic effects of the formulations were evaluated using the von Frey filament test in a mouse model of diabetic neuropathy (DN). The PLO gel showed the highest permeability of pregabalin, followed by the aqueous solution, and no permeation was observed in the two cream formulations. The MS imaging analysis showed that pregabalin was distributed up to the dermis in the PLO gel 1 h after application, while the aqueous solution was distributed near the epidermis. A significant analgesic effect (p <.05) was observed 1.5 h after PLO gel application in the DN model mice, but the aqueous solution had no effect. This study indicated for the first time that pregabalin penetrated beyond the skin epidermis up to the dermis, from the PLO gel formulation, and that the application of this formulation exhibited an in vivo analgesic effect in the mouse model of DN. 2022-08-04T04:42:31Z 2022-08-04T04:42:31Z 2022-04-01 Article Pharmacology Research and Perspectives. Vol.10, No.2 (2022) 10.1002/prp2.919 20521707 2-s2.0-85126881630 https://repository.li.mahidol.ac.th/handle/123456789/75192 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85126881630&origin=inward
institution Mahidol University
building Mahidol University Library
continent Asia
country Thailand
Thailand
content_provider Mahidol University Library
collection Mahidol University Institutional Repository
topic Neuroscience
Pharmacology, Toxicology and Pharmaceutics
spellingShingle Neuroscience
Pharmacology, Toxicology and Pharmaceutics
Michiru Nagao
Masataka Tajima
Erika Sugiyama
Ryosuke Shinouchi
Keita Shibata
Masayuki Yoshikawa
Takushi Yamamoto
Vilasinee Hirunpanich Sato
Koji Nobe
Hitoshi Sato
Evaluation of in vitro transdermal permeation, mass spectrometric imaging, and in vivo analgesic effects of pregabalin using a pluronic lecithin organogel formulation in mice
description In clinical practice, pregabalin is orally administered for neuropathic pain, but causes severe central nervous system side effects, such as dizziness, which results in dose limitation or discontinuation. To reduce the central side effects of pregabalin, we developed four pregabalin preparations for transdermal application: 0.4% aqueous solution, pluronic lecithin organogel (PLO gel), hydrophilic cream, and lipophilic cream. Transdermal permeabilities of pregabalin among the four formulations were compared in vitro using hairless mouse skin. The longitudinal distribution of pregabalin within the skin was analyzed using mass spectrometric (MS) imaging. Furthermore, the in vivo analgesic effects of the formulations were evaluated using the von Frey filament test in a mouse model of diabetic neuropathy (DN). The PLO gel showed the highest permeability of pregabalin, followed by the aqueous solution, and no permeation was observed in the two cream formulations. The MS imaging analysis showed that pregabalin was distributed up to the dermis in the PLO gel 1 h after application, while the aqueous solution was distributed near the epidermis. A significant analgesic effect (p <.05) was observed 1.5 h after PLO gel application in the DN model mice, but the aqueous solution had no effect. This study indicated for the first time that pregabalin penetrated beyond the skin epidermis up to the dermis, from the PLO gel formulation, and that the application of this formulation exhibited an in vivo analgesic effect in the mouse model of DN.
author2 Shimadzu Corporation
author_facet Shimadzu Corporation
Michiru Nagao
Masataka Tajima
Erika Sugiyama
Ryosuke Shinouchi
Keita Shibata
Masayuki Yoshikawa
Takushi Yamamoto
Vilasinee Hirunpanich Sato
Koji Nobe
Hitoshi Sato
format Article
author Michiru Nagao
Masataka Tajima
Erika Sugiyama
Ryosuke Shinouchi
Keita Shibata
Masayuki Yoshikawa
Takushi Yamamoto
Vilasinee Hirunpanich Sato
Koji Nobe
Hitoshi Sato
author_sort Michiru Nagao
title Evaluation of in vitro transdermal permeation, mass spectrometric imaging, and in vivo analgesic effects of pregabalin using a pluronic lecithin organogel formulation in mice
title_short Evaluation of in vitro transdermal permeation, mass spectrometric imaging, and in vivo analgesic effects of pregabalin using a pluronic lecithin organogel formulation in mice
title_full Evaluation of in vitro transdermal permeation, mass spectrometric imaging, and in vivo analgesic effects of pregabalin using a pluronic lecithin organogel formulation in mice
title_fullStr Evaluation of in vitro transdermal permeation, mass spectrometric imaging, and in vivo analgesic effects of pregabalin using a pluronic lecithin organogel formulation in mice
title_full_unstemmed Evaluation of in vitro transdermal permeation, mass spectrometric imaging, and in vivo analgesic effects of pregabalin using a pluronic lecithin organogel formulation in mice
title_sort evaluation of in vitro transdermal permeation, mass spectrometric imaging, and in vivo analgesic effects of pregabalin using a pluronic lecithin organogel formulation in mice
publishDate 2022
url https://repository.li.mahidol.ac.th/handle/123456789/75192
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