Influence of chemical penetration enhancers on skin permeability of ellagic acid-loaded niosomes

This study aimed to develop niosomes of ellagic acid (EA), a potent antioxidant phytochemical substance, for dermal delivery and to investigate the influence of chemical penetration enhancers on the physicochemical properties of EA-loaded niosomes. The EA niosomes were prepared by reverse phase evaporation method using Span 60, Tween 60 and cholesterol as vesicle forming agents and Solulan C24 as a steric stabilizer. Polyethylene glycol 400 (PEG) was used as a solubilizer while dimethylsulfoxide (DMSO) or N-methyl-2-pyrrolidone (NMP) was used as a skin penetration enhancer. It was found that the mean particle sizes of EA-loaded niosomes were in the range of 312–402 nm with PI values of lower than 0.4. The niosomes were determined to be spherical multilamellar vesicles as observed by transmission electron microscope and optical microscopy. All niosomes were stable after 4 months storage at 4 °C. In vitro skin permeation through human epidermis revealed that the skin enhancers affected the penetration of EA from the niosomes at 24 h. The DMSO niosomes showed the highest EA amount in epidermis; whereas the NMP niosomes had the highest EA amount in the acceptor medium. Concomitantly, the skin distribution by confocal laser scanning microscopy showed the high fluorescence intensity of the DMSO niosomes and NMP niosomes at a penetration depth of between 30–90 μm (the epidermis layer) and 90–120 μm (the dermis layer) under the skin, respectively. From the results, it can be concluded that the DMSO niosomes are suitable for epidermis delivery of EA while the NMP niosomes can be used for dermis delivery of EA.