TY  - JOUR
SN  - 03785173
PB  - Elsevier B.V.
EP  - 38
AV  - none
N1  - cited By 65
SP  - 31
TI  - Characterization and cytotoxicity evaluation of biocompatible amino acid esters used to convert salicylic acid into ionic liquids
Y1  - 2018///
UR  - https://www.scopus.com/inward/record.uri?eid=2-s2.0-85047271527&doi=10.1016%2fj.ijpharm.2018.05.021&partnerID=40&md5=e6b2e5435aa4949bbb4ffa718024e2bd
A1  - Moshikur, R.M.
A1  - Chowdhury, M.R.
A1  - Wakabayashi, R.
A1  - Tahara, Y.
A1  - Moniruzzaman, M.
A1  - Goto, M.
JF  - International Journal of Pharmaceutics
VL  - 546
N2  - The technological utility of active pharmaceutical ingredients (APIs) is greatly enhanced when they are transformed into ionic liquids (ILs). API-ILs have better solubility, thermal stability, and the efficacy in topical delivery than solid or crystalline drugs. However, toxicological issue of API-ILs is the main challenge for their application in drug delivery. To address this issue, 11 amino acid esters (AAEs) were synthesized and investigated as biocompatible counter cations for the poorly water-soluble drug salicylic acid (Sal) to form Sal-ILs. The AAEs were characterized using 1H and 13C NMR, FTIR, elemental, and thermogravimetric analyses. The cytotoxicities of the AAE cations, Sal-ILs, and free Sal were investigated using mammalian cell lines (L929 and HeLa). The toxicities of the AAE cations greatly increased with inclusion of long alkyl chains, sulfur, and aromatic rings in the side groups of the cations. Ethyl esters of alanine, aspartic acid, and proline were selected as a low cytotoxic AAE. The cytotoxicities of the Sal-ILs drastically increased compared with the AAEs on incorporation of Sal into the cations, and were comparable to that of free Sal. Interestingly, the water miscibilities of the Sal-ILs were higher than that of free Sal, and the Sal-ILs were miscible with water at any ratio. A skin permeation study showed that the Sal-ILs penetrated through skin faster than the Sal sodium salt. These results suggest that AAEs could be used in biomedical applications to eliminate the use of traditional toxic solvents for transdermal delivery of poorly water-soluble drugs. © 2018 Elsevier B.V.
IS  - 1-2
KW  - amino acid derivative; amino acid ester derivative; ionic liquid; salicylic acid; unclassified drug; amino acid; ester; ionic liquid; salicylic acid
KW  -  animal tissue; Article; biocompatibility; carbon nuclear magnetic resonance; drug cytotoxicity; drug synthesis; elemental analysis; female; Fourier transform infrared spectroscopy; HeLa cell line; human; human cell; NCTC clone 929 cell line; nonhuman; priority journal; proton nuclear magnetic resonance; skin permeability; thermogravimetry; Yucatan micropig; animal; cell line; cell survival; chemistry; cutaneous drug administration; drug effect; in vitro study; metabolism; mouse; pig; skin; skin absorption
KW  -  Administration
KW  -  Cutaneous; Amino Acids; Animals; Cell Line; Cell Survival; Esters; Female; HeLa Cells; Humans; In Vitro Techniques; Ionic Liquids; Mice; Salicylic Acid; Skin; Skin Absorption; Swine
ID  - scholars10115
ER  -