Transdermal delivery of dimethyl fumarate for Alzheimer's disease: Effect of penetration enhancers

Dimethyl fumarate (DMF) is an orally administered drug with neuroprotective and immunomodulatory activities. It has potential uses in the treatment of neurodegenerative diseases such as Alzheimer's disease (AD). The objective of this study was to investigate the feasibility of transdermal delivery of DMF by studying the effect of different penetration enhancers on the skin permeation of DMF. The permeation of saturated DMF solutions was investigated in propylene glycol (PG) with varying concentrations of each of the following enhancers: Polysorbate 80 (T80), N-methyl pyrrolidone (NMP), laurocapram (Azone (R)) (Az), Transcutol P (Tc), Terpineol (Terp), and cineole (Cin) using vertical Franz diffusion cells and human cadaver skin. The results showed that all penetration enhancers improved the rate of permeation of DMF. The rank order for the highest concentration of each enhancer was as follows: Cin > Az > TC > Terp> T80 >= NMP. The most effective penetration enhancer was shown to be 5% cineole with a 5.3-fold increase in the enhancement ratio (ER). The amounts of drug delivered suggest that DMF is a potential candidate for transdermal drug delivery. (C) 2017 Elsevier B.V. All rights reserved.