title: Ionic liquid-in-oil microemulsion as a potential carrier of sparingly soluble drug: characterization and cytotoxicity evaluation.
abstract: Pharmaceutical industries have posed challenges in the topical and transdermal administration of drugs which are poorly soluble or insoluble in water and most of organic solvents. In an approach to overcome this limitation, ionic liquid-in-oil (IL/o) microemulsions (MEs) were employed to increase the solubility of a sparingly soluble drug to enhance its topical and transdermal delivery. The formulation of MEs was composed of a blend of nonionic surfactants, polyoxyethylene sorbitan monooleate (Tween-80) and sorbitan laurate (Span-20), isopropyl myristate (IPM) as an oil phase, and IL [C(1)mim] [(CH(3)O)(2)PO(2)] (dimethylimidazolium dimethylphosphate) as a pseudophase. Among various weight ratios of Tween-80 to Span-20 investigated in the ME systems, the ratio 3:2 showed excellent solubility and skin permeation enhancing effect for acyclovir (ACV) used as a model sparingly soluble drug. The size and size distribution of the ME droplets with and without drug were determined by dynamic light scattering. The permeability study of ACV incorporated in IL droplets as well as other formulations was performed into and across the Yucatan micropig (YMP) porcine skin, and the use of IL/o MEs has been shown to dramatically increase ACV administration. Finally, the cytotoxicity of the new carrier was evaluated in vitro using the reconstructed human epidermal model LabCyte™ EPI-MODEL12. It was found that the cell viability of IL/o MEs containing 4wt% IL was over 80% compared to Dulbecco's Phosphate-Buffered Salines, indicating low cytotoxicity of the carrier. Taken together these results, it can be assumed that IL-assisted nonaqueous ME could serve as a versatile and efficient nanodelivery system for insoluble or sparingly soluble drug molecules that require solubilizing agents for delivery.
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Kyushu University, 744 Moto-oka, Fukuoka 819-0395, Japan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Moniruzzaman
authors.forename: Miki
authors.initials: M
authors.lastname: Tamura
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Tahara
authors.forename: Noriho
authors.initials: N
authors.lastname: Kamiya
authors.forename: Masahiro
authors.initials: M
authors.lastname: Goto
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage / Q000493:pharmacokinetics; D000279:Administration, Cutaneous; D000818:Animals; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D004355:Drug Stability; D045703:Emulsifying Agents / Q000737:chemistry*; D004655:Emulsions; D005260:Female; D006601:Hexoses / Q000737:chemistry; D006801:Humans; D052578:Ionic Liquids / Q000737:chemistry*; D009226:Myristates / Q000737:chemistry; D010316:Particle Size; D010539:Permeability; D011136:Polysorbates / Q000737:chemistry; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D023422:Skin Irritancy Tests; D012995:Solubility; D013552:Swine; D013556:Swine, Miniature
chemical_list: D004337:Drug Carriers; D045703:Emulsifying Agents; D004655:Emulsions; D006601:Hexoses; D052578:Ionic Liquids; D009226:Myristates; D011136:Polysorbates; C008205:isopropyl myristate; C014822:sorbitan monolaurate; D000212:Acyclovir