文献类型：期刊文献

英文题名：Transdermal Delivery of Metformin Utilizing Ionic Liquid Technology: Insight Into the Relationship Between Counterion Structures and Properties

作者：Hong, Minghuang[1,2,3,4];Wang, Qinglin[2,3,4];Wang, Kai[2,3,4];Li, Jinghui[2,3,4];Qi, Ming-Hui[2,3,4];Ren, Guo-Bin[1,2,3,4]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[2]Shanghai Frontier Sci Res Base Optogenet Tech Cel, Shanghai 200237, Peoples R China;[3]Lab Pharmaceut Crystal Engn & Technol, 130 Meilong Rd, Shanghai 200237, Peoples R China;[4]East China Univ Sci & Technol, Minist Educ, Engn Res Ctr Pharmaceut Proc Chem, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2022

卷号：39

期号：10

起止页码：2459

外文期刊名：PHARMACEUTICAL RESEARCH

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000861130800001)】；

基金：This work was sponsored by Natural Science Foundation of Shanghai (No. 20ZR1413600), the National Natural Science Foundation of China (No. 21576080) and Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission).

语种：英文

外文关键词：counterion structure; delivery system; ionic liquids; metformin; skin permeability; transdermal drug

摘要：Purpose The purpose of the present study was to explore the feasibility of transdermal delivery of metformin, a commonly used oral antidiabetic drug, by ionic liquid (IL) technology. Methods Metformin hydrochloride (MetHCl) was first transformed into three kinds of ILs with different counterions. The physicochemical properties of the obtained ILs were characterized in depth. The simulation of stable configuration and calculation of interaction energies were conducted based on density functional theory (DFT). Skin-PAMPA was used to evaluate the intrinsic transdermal permeation properties. The cytotoxicity assay of these ILs was conducted using HaCaT cells to evaluate the toxicity to skin. These metformin ILs were then formulated into transdermal patch, and the transdermal potential was further evaluated using in vitro dissolution test and skin permeation assay. Finally, the pharmacokinetic profiles of these metformin IL-containing patches were determined. Results Among all the three Met ILs, metformin dihexyl sulfosuccinate (MetDH) with proper overall physiochemical and biological properties demonstrated the highest relative bioavailability. Metformin docusate (MetD) with the highest lipophilicity and intrinsic transdermal permeability exhibited the most significant sustained release profile in vivo. Both MetDH and MetD were the promising candidates for further clinical investigations. Conclusions Overall, the properties of ILs were closely related to the structures of counterion. IL technology provided the opportunities to finely tune the solid-state and biological properties of Metformin and facilitated the successful delivery by transdermal route.