Innovative bola-surfactant niosomes as topical delivery systems of 5-fluorouracil for the treatment of skin cancer

An innovative niosomal system made up of α,ω-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 ∼400 nm, which were reduced to ∼200 nm by a sonication procedure with a polydispersion index value of 0.1. Bola-niosomes showed a loading capacity of ∼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.