TY  - JOUR
A1  - Md Moshikur, R.
A1  - Shimul, I.M.
A1  - Uddin, S.
A1  - Wakabayashi, R.
A1  - Moniruzzaman, M.
A1  - Goto, M.
JF  - ACS Applied Materials and Interfaces
UR  - https://www.scopus.com/inward/record.uri?eid=2-s2.0-85144506615&doi=10.1021%2facsami.2c15636&partnerID=40&md5=57d340b7a7c3873d70a546a596a84c5b
VL  - 14
Y1  - 2022///
IS  - 50
N2  - The transdermal delivery of hydrophilic drugs remains challenging owing to their poor ability to permeate the skin; formulation with oil media is difficult without adding chemical permeation enhancers or co-solvents. Herein, we synthesized 12 oil-miscible ionic liquid (IL) drugs comprising lidocaine-, imipramine-, and levamisole (Lev)-hydrochloride with fatty acid permeation enhancers, i.e., laurate, oleate, linoleate, and stearate as counterions. A set of in vitro and in vivo studies was performed to investigate the potency and deliverability of the transdermal drug formulations. All of the synthesized compounds were freely miscible with pharmaceutically acceptable solvents/agents (i.e., ethanol, N-methyl pyrrolidone, Tween 20, and isopropyl myristate (IPM)). In vitro permeation studies revealed that the oleate-based Lev formulation had 2.6-fold higher skin permeation capability than the Lev salts and also superior ability compared with the laurate-, linoleate-, and stearate-containing samples. Upon in vivo transdermal administration to mice, the peak plasma concentration, elimination half-life, and area under the plasma concentration curve values of Lev-IL were 4.6-, 2.9-, and 5.4-fold higher, respectively, than those of the Lev salt. Furthermore, in vitro skin irritation and in vivo histological studies have demonstrated that Lev-IL has excellent biocompatibility compared with a conventional ionic liquid-based carrier. The results indicate that oil-miscible IL-based drugs provide a simple and scalable strategy for the design of effective transdermal drug delivery systems. © 2022 American Chemical Society.
ID  - scholars16053
KW  - Biocompatibility; Controlled drug delivery; Fatty acids; Hydrophilicity; Mammals; Organic solvents; Pharmacokinetics; Targeted drug delivery
KW  -  Biocompatible; Hydrophilic drugs; In-vitro; In-vivo; Laurate; Permeation enhancers; Plasma concentration; Skin permeation; Synthesised; Transdermal delivery
KW  -  Ionic liquids
KW  -  drug carrier; ionic liquid; lauric acid; linoleic acid; oleic acid; solvent; stearic acid
KW  -  animal; chemistry; cutaneous drug administration; drug delivery system; mouse; permeability; procedures; skin; skin absorption
KW  -  Administration
KW  -  Cutaneous; Animals; Drug Carriers; Drug Delivery Systems; Ionic Liquids; Laurates; Linoleic Acid; Mice; Oleic Acid; Permeability; Skin; Skin Absorption; Solvents; Stearates
EP  - 55341
PB  - American Chemical Society
SN  - 19448244
N1  - cited By 6
SP  - 55332
TI  - Transformation of Hydrophilic Drug into Oil-Miscible Ionic Liquids for Transdermal Drug Delivery
AV  - none
ER  -