Development of Novel Ionic Liquid-Based Microemulsion Formulation for Dermal Delivery of 5-Fluorouracil

Abstract

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.KEY WORDS: 5-fluorouracil; dermal delivery; ionic liquids; ionic liquid in oil (IL/o) microemulsion; skin cancer.

Design and characterisation of colloidal nanocarriers for enhanced skin delivery of etodolac

“…Furthermore, ETD loaded microemulsion formulations exhibited high linear regression (r 2 >0.99) values between shear stress and shear rate, indicating Newtonian's flow behaviour (Figure 2). They also had low viscosity values in range of 26.09±0.22 and 38.26±0.26 mPa.s (Table 1), which is one of microemulsion characteristics, as reported in the previous studies [30][31][32]. The morphological structure of ETD loaded ME3 formulation (as a representative formulation of microemulsions) was observed by TEM.…”

Ionic Liquids in Drug Delivery

“…The use of ILs as alternative solvents to this purpose was first introduced by Jaitely et al [36], in 2008, when using imidazolium-based ILs to solubilize potassium penicillin V, dexamethasone, dehydroepiandrosterone and progesterone. After this, several studies reported solubility enhancements by several orders of magnitude for antifungal [35,37,38], analgesic [35], non-steroidal anti-inflammatory [39,40], and anti-cancer [17,41] drugs when using ILs and compared to their water solubility.…”

In Vitro Evaluation of Self-Nano-Emulsifying Drug Delivery Systems (SNEDDS) Containing Room Temperature Ionic Liquids (RTILs) for the Oral Delivery of Amphotericin B

“…Significantly higher solubilities were obtained when replacing 33% of SNEDDS with RTILs (1.55-fold for SNEDDS:BMIMBF 4 , 1.73-fold for SNEDDS:BMIMPF 6 and 2.52-fold for SNEDDS:HMIMCl respectively) (p < 0.05). This might be attributed to the fact that the PF 6 salts are more hydrophobic than the BF 4 salts [24] and therefore are expected to dissolve AmpB better. In addition, the high solubility of AmpB with HMIMCl might be attributed to the longer alkyl chain (hexyl-versus butyl-for the other two) in the imidazolium cation.…”

“…Finally, the co-aggregation of the solute with the hydrotropes above a minimum hydrotrope concentration has been proposed as the most likely mechanism [21,22]. On the other hand, RTILs have generated considerable interest in fields as broad as catalysis, extraction, energy storage and CO 2 capture, but also in skin delivery as permeation enhancers [23,24].…”