title: Development of novel ionic liquid-based microemulsion formulation for dermal delivery of 5-Fluorouracil.
abstract: 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.
authors.affiliation: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India, shishugoindi@yahoo.co.in.
authors.forename: Shishu
authors.initials: S
authors.lastname: Goindi
authors.forename: Prabhleen
authors.initials: P
authors.lastname: Arora
authors.forename: Neeraj
authors.initials: N
authors.lastname: Kumar
authors.forename: Ashana
authors.initials: A
authors.lastname: Puri
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D004655:Emulsions / Q000737:chemistry*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000737:chemistry*; D006601:Hexoses / Q000737:chemistry; D007093:Imidazoles / Q000737:chemistry; D052578:Ionic Liquids / Q000737:chemistry*; D051379:Mice; D009226:Myristates / Q000737:chemistry; D009821:Oils / Q000737:chemistry; D010539:Permeability; D011136:Polysorbates / Q000737:chemistry; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D006601:Hexoses; D007093:Imidazoles; D052578:Ionic Liquids; D009226:Myristates; D009821:Oils; D011136:Polysorbates; D013501:Surface-Active Agents; D014867:Water; C008205:isopropyl myristate; C502841:1-butyl-3-methylimidazolium chloride; C014822:sorbitan monolaurate; D005472:Fluorouracil