Open AccessEvaluation of in vitro transdermal permeation, mass spectrometric imaging, and in vivo analgesic effects of pregabalin using a pluronic lecithin organogel formulation in mice
Author(s) -
Nagao Michiru,
Tajima Masataka,
Sugiyama Erika,
Shinouchi Ryosuke,
Shibata Keita,
Yoshikawa Masayuki,
Yamamoto Takushi,
Sato Vilasinee Hirunpanich,
Nobe Koji,
Sato Hitoshi
Publication year - 2022
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.919
Subject(s) - pregabalin , in vivo , transdermal , poloxamer , analgesic , permeation , lecithin , pharmacology , chemistry , dermis , poloxamer 407 , pharmacokinetics , chromatography , ex vivo , medicine , in vitro , anesthesia , biochemistry , pathology , membrane , microbiology and biotechnology , organic chemistry , copolymer , biology , polymer
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.