Chemoprevention of skin cancer using low HLB surfactant nanoemulsion of 5-fluorouracil: a preliminary study

Abstract

Oral delivery of 5-fluorouracil (5-FU) is difficult due to its serious adverse effects and extremely low bioavailability. Therefore, the aim of present investigation was to develop and evaluate low HLB surfactant nanoemulsion of 5-FU for topical chemoprevention of skin cancer. Low HLB surfactant nanoemulsions were prepared by oil phase titration method. Thermodynamically stable nanoemulsions were characterized in terms of droplet size distribution, zeta potential, viscosity and refractive index. Selected formulations and control were subjected to in vitro skin permeation studies through rat skin using Franz diffusion cells. Optimized formulation F9 was subjected to stability and in vitro cytotoxic studies on melanoma cell lines. Enhancement ratio was found to be 22.33 in formulation F9 compared with control and other formulations. The values of steady state flux and permeability coefficient for formulation F9 were found to be 206.40 AE 14.56 mg cm À2 h À1 and 2.064 Â 10 À2 AE 0.050 Â 10 À2 cm h À1, respectively. Optimized formulation F9 was found to be physical stable. In vitro cytotoxicity studies on SK-MEL-5 cancer cells indicated that 5-FU in optimized nanoemulsion is much more efficacious than free 5-FU. From these results, it can be concluded that the developed nanoemulsion might be a promising vehicle for chemoprevention of skin cancer.

Removal of glibenclamide from aqueous solution using water/PEG-400/ethanol/eucalyptus oil green nanoemulsions

“…The RIs of all formulations were very close to the reported RI of EO, indicating the w/o type behavior of all nanoemulsions. These results were in accordance with our previous reports [13,14,25,26].…”

“…Pseudo-ternary phase diagrams were developed by oil phase titration method to identify nanoemulsion zones as reported in literature [25,26]. The results are presented in Fig.…”

“…The mean droplet size and PI of nanoemulsions (E 1 -E 5 ) were recorded using Malvern Particle Size Analyzer (Malvern Instruments Ltd., Holtsville, NY) [25]. The viscosity of nanoemulsions (E 1 -E 5 ) was recorded at room temperature (25 ± 0.5°C) using Brookfield Viscometer (Brookfield Engineering Laboratories, Inc., Middleboro, MA) [26]. The RI of nanoemulsions (E 1 -E 5 ) and pure oil (EO) was recorded at room temperature using Abbes type Refractometer (Precision Standard Testing Equipment Corporation, Germany) [25,26].…”

“…Water-in-oil (w/o) type nanoemulsions were prepared by oil phase titration method as reported in literature [25,26]. PEG-400 (surfactant) and ethanol (cosurfactant) were mixed in the mass ratios of 1:2, 1:1, 2:1 and 3:1.…”

“…Various thermodynamic stability tests were performed by subjecting nanoemulsions to centrifugation, heating & cooling cycles and freeze-pump-thaw cycles [13,14,26]. The mean droplet size and PI of nanoemulsions (E 1 -E 5 ) were recorded using Malvern Particle Size Analyzer (Malvern Instruments Ltd., Holtsville, NY) [25].…”