Innovative bola-surfactant niosomes as topical delivery systems of 5-fluorouracil for the treatment of skin cancer.
An innovative niosomal system made up of alpha,omega-hexadecyl-bis-(1-aza-18-crown-6) (Bola), Span 80 and cholesterol (2:5:2 molar ratio) was proposed as a topical delivery system for 5-fluorouracil (5-FU), largely used in the treatment of different forms of skin cancers. Bola-niosomes showed a mean size of approximately 400 nm, which were reduced to approximately 200 nm by a sonication procedure with a polydispersion index value of 0.1. Bola-niosomes showed a loading capacity of approximately 40% with respect to the amount of 5-FU added during the preparation. 5-FU-loaded bola-niosomes were tested on SKMEL-28 (human melanoma) and HaCaT (non-melanoma skin cancer with a specific mutations in the p53 tumor suppressor gene) to assess the cytotoxic activity with respect to the free drug. 5-FU-loaded bola-niosomes showed an improvement of the cytotoxic effect with respect to the free drug. Confocal laser scanning microscopy studies were carried out to evaluate both the extent and the time-dependent bola-niosome-cell interaction. The percutaneous permeation of 5-FU-loaded niosomes was evaluated by using human stratum corneum and epidermis membranes. Bola-niosomes provided an increase of the drug penetration of 8- and 4-folds with respect to a drug aqueous solution and to a mixture of empty bola-niosomes with a drug aqueous solution.
Paolino
Donatella
D
Department of Experimental and Clinical Medicine, Faculty of Medicine, University Magna Graecia of Catanzaro, Campus Universitario, Building of BioSciences, Viale Europa, Germaneto (CZ), Italy.
Cosco
Donato
D
Muzzalupo
Rita
R
Trapasso
Elena
E
Picci
Nevio
N
Fresta
Massimo
M
D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D005472:Fluorouracil / Q000008:administration & dosage*; D006601:Hexoses / Q000008:administration & dosage*; D006801:Humans; D008081:Liposomes; D012878:Skin Neoplasms / Q000188:drug therapy*; D013501:Surface-Active Agents / Q000008:administration & dosage*
D000964:Antimetabolites, Antineoplastic; D006601:Hexoses; D008081:Liposomes; D013501:Surface-Active Agents; C018665:sorbitan monooleate; D005472:Fluorouracil