title: 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 ± 14.56 µg cm(-2) h(-1) and 2.064 × 10(-2) ± 0.050 × 10(-2 )cm h(-1), 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.
authors.affiliation: Center of Excellence in Biotechnology Research .
authors.forename: Faiyaz
authors.initials: F
authors.lastname: Shakeel
authors.forename: Nazrul
authors.initials: N
authors.lastname: Haq
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al-Dhfyan
authors.forename: Fars K
authors.initials: FK
authors.lastname: Alanazi
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Alsarra
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D018890:Chemoprevention / Q000379:methods; D016503:Drug Delivery Systems; D004355:Drug Stability; D004655:Emulsions; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008545:Melanoma / Q000517:prevention & control*; D053758:Nanoparticles; D010316:Particle Size; D051381:Rats; D012869:Skin Absorption; D012878:Skin Neoplasms / Q000517:prevention & control*; D013816:Thermodynamics
chemical_list: D000964:Antimetabolites, Antineoplastic; D004655:Emulsions; D005472:Fluorouracil
keywords: 5-Fluorouracil; chemoprevention; low HLB surfactant; nanoemulsion; transdermal delivery