The present study was aimed at synthesizing an
imidazole-based
ionic liquid 1-butyl-3-methylimidazolium bromide (BMIMBr) and subsequent development of a novel
ionic liquid-in-oil (IL/o) microemulsion (ME) system for dermal delivery of a poorly permeating
drug 5-fluorouracil (5-FU). A significant enhancement in the solubility of
5-FU was observed in BMIMBr. IL/o MEs of
5-FU were prepared using
isopropyl myristate,
Tween 80/
Span 20, and BMIMBr. Results of ex vivo skin permeation studies through mice skin indicated that the selected IL/o ME exhibited 4-fold enhancement in percent
drug permeation as compared to aqueous
solution, 2.3-fold as compared to hydrophilic
ointment, and 1.6-fold greater permeation than water in oil (w/o) ME. The results of in vivo studies against dimethylbenz(a)
anthracene (DMBA)/12-O-tetradecanoylphorbol-13-
acetate (TPA)-induced mice skin
carcinogenesis demonstrated that the IL/o ME could effectively treat
skin cancer in 4 weeks. In addition, the side effects such as
erythema and irritation associated with the conventional formulations were not observed. Histopathological studies showed that the use of IL/o ME caused no anatomic and pathological changes in the skin structure of mice. These studies suggest that the use of IL-based ME system can efficiently enhance the solubility and permeability of
5-FU and hence its therapeutic efficacy.