Journal
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
Volume 8, Issue 16, Pages 6263-6272Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acssuschemeng.9b07773
Keywords
Surface-active ionic liquid; Microemulsion; Drug solubility; Physical stability; Cytotoxicity
Categories
Funding
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [JP19H05518]
- Government of Japan (MEXT, Japan)
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Developing a universal drug delivery vehicle of sparingly soluble drugs remains a challenge, with surface-active ionic liquid (SAIL)-based ionic liquid-in-oil (IL/O) microemulsions (MEs) being the most suitable vehicles. In this study, a series of SAILs were formulated to prepare novel IL/O MEs composed of SAIL, sorbitan laurate (Span-20), and isopropyl myristate. On the basis of the constructed pseudoternary diagrams, the SAILs played vital surfactant roles with Span-20 acting as a cosurfactant. Excellent drug solubility of MEs prepared with a ratio of 2:1 (SAIL[Cho][Ole]:Span-20) was observed. Examination of the droplet shape, size, and size distribution of the MEs revealed well-distributed particle sizes of 6.5-21.2 nm that formed spherical micelles with the IL 1,3-dimethylimidazolium dimethyl phosphate at the core of the MEs. The MEs showed excellent solubility of sparingly soluble drugs (i.e., celecoxib, acyclovir, methotrexate, and dantrolene sodium). In vitro cytotoxicity of the new carrier using a three-dimensional reconstructed human epidermis model revealed that the cell viability of SAIL-based MEs (94%) was similar when compared to conventional Tween-80-based MEs (96%) at the same IL concentration (4%). The results indicate that the SAIL surfactant in the MEs represents a potential alternative to conventional surfactants for solubilizing insoluble drug molecules.
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