title: Topical Delivery of 5-Fluorouracil from Pheroid™ Formulations and the In Vitro Efficacy Against Human Melanoma.
abstract: Drug delivery vehicles can influence the topical delivery and the efficacy of an active pharmaceutical ingredient (API). In this study, the influence of Pheroid™ technology, which is a unique colloidal drug delivery system, on the skin permeation and antimelanoma efficacy of 5-fluorouracil were investigated. Lotions containing Pheroid™ with different concentrations of 5-fluorouracil were formulated then used in Franz cell skin diffusion studies and tape stripping. The in vitro efficacy of 5-fluorouracil against human melanoma cells (A375) was investigated using a flow cytometric apoptosis assay. Statistically significant concentrations of 5-fluorouracil diffused into and through the skin with Pheroid™ formulations resulting in an enhanced in vitro skin permeation from the 4.0% 5-fluorouracil lotion (p < 0.05). The stratum corneum-epidermis and epidermis-dermis retained 5-fluorouracil concentrations of 2.31 and 6.69 μg/ml, respectively, after a diffusion study with the 4.0% Pheroid™ lotion. Subsequent to the apoptosis assay, significant differences were observed between the effect of 13.33 μg/ml 5-fluorouracil in Pheroid™ lotion and the effects of the controls. The results obtained suggest that the Pheroid™ drug delivery system possibly enhances the flux and delivery of 5-fluorouracil into the skin. Therefore, using Pheroid™ could possibly be advantageous with respect to topical delivery of 5-fluorouracil.
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.
authors.forename: Tawona N
authors.initials: TN
authors.lastname: Chinembiri
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.
authors.forename: Minja
authors.initials: M
authors.lastname: Gerber
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.
authors.forename: Lissinda
authors.initials: L
authors.lastname: du Plessis
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.
authors.forename: Jan
authors.initials: J
authors.lastname: du Preez
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa. Jeanetta.DuPlessis@nwu.ac.za.
authors.forename: Jeanetta
authors.initials: J
authors.lastname: du Plessis
mesh_terms: D000279:Administration, Cutaneous; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D004817:Epidermis / Q000378:metabolism; D005079:Excipients / Q000737:chemistry; D005472:Fluorouracil / Q000008:administration & dosage* / Q000737:chemistry*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy*; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption
chemical_list: D005079:Excipients; D005472:Fluorouracil
keywords: A375 cells; cell culture; flow cytometry; melanoma; permeation enhancer