Ionic liquids (IL) technology provides a useful platform to achieve the topical delivery of therapeutic agents, because of its capability to improve skin permeability. While the majority of the researches aimed to achieve local action by topical IL delivery, systemic action of therapeutic agents by local topical application has rarely been reported. In the present work, Gliclazide (GLI), a second-generation sulfonylurea drug was transformed into an IL with tributyl(tetradecyl)phosphonium for the first time. The physicochemical properties of this IL were systematically characterized by DSC, TGA, FT-IR, NMR, and HPLC. The transdermal patch based on this IL was further prepared using DURO-TAK®87-4098. The fabricated gliclazide based ionic liquid [P6,6,6,14][GLI] transdermal patch displayed satisfactory in vitro and in vivo performance. The [P6,6,6,14][GLI] patch released 88.17% of the loaded drug within a 3-day period in the in vitro dissolution test, confirming its sustained release property. Meanwhile, GLI effectively permeated through the artificial skin from [P6,6,6,14][GLI] transdermal patch in the in vitro skin permeation test, with the permeation rate and lag time of 16.571 ± 0.328 μg/cm2/h and 3.027 ± 0.154 h respectively. The [P6,6,6,14][GLI] transdermal patch showed favorable PK profile in rat as compared with GLI oral suspension. The relative bioavailability of GLI reached 92.06% of GLI oral suspension, while the Cmax was significantly reduced. Most importantly, [P6,6,6,14][GLI] transdermal patch demonstrated superior hypoglycemic effect to the oral suspension both in the fasted and fed condition, confirming the feasibility of systemic action by local topical delivery of IL. In addition, the [P6,6,6,14][GLI] transdermal patch caused no skin irritation based on histopathological analysis.
Keywords: Diabetes mellitus; Gliclazide; Hypoglycemic effect; Ionic liquid; Transdermal drug delivery.
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