Topical nano-delivery of 5-fluorouracil: Preparation and characterization of water-in-oil nanoemulsion

Purpose: To prepare and characterize a water-in-oil nanoemulsion of 5-fluorouracil (5FU) for enhanced skin penetration.
Methods: Nanoemulsions of 5FU were prepared using Capyrol (propylene glycol monocaprylate). Transcutol (highly purified diethylene glycol monoethyl ether) and polyethylene glycol (PEG) 400 as oil, surfactant and co-surfactant, respectively. The optimized formulations were subjected to heating -cooling cycling, centrifugation and freeze - thaw cycling to assess their stability. Particle size distribution and zeta potential of the nanoemulsions were evaluated. Furthermore, in vitro and in vivo skin permeation studies were carried out on the formulations in a rat model. Skin irritation studies were also performed on rats to assess the irritation potential of the formulations. The 1 % w/v of Carbopol 934 gel loaded with 1 % 5FU was used as control (FU gel).
Results: The results showed that the mean droplet size of the nanoemulsions was ~100 nm with a zeta potential of ± 15. Significant increase in permeability was also observed for the nanoemulsion formulations compared with control. The steady-state flux (Jss), enhancement ratio and permeability coefficient (Kp) for optimized nanoemulsion formulation were significantly (p < 0.05) higher than those of the conventional gel (control). Both in vitro and in vivo skin retention results indicate higher drug release from the nanoemulsion (292.45 μg/cm²) than for control (121.42 μg/cm²). Mean irritation index for the nanoemulsion was significantly lower than for control.
Conclusion: The results suggest that a water-in-oil nanoemulsion is safe and can potentially be used to promote skin penetration of 5FU following topical application on the skin for the treatment of some skin diseases.

Keywords
Nanoemulsion; Controlled release; 5-Fluorouracil; Skin penetration; Skin irritation