Synergistic effects of ethosomes and chemical enhancers on enhancement of naloxone permeation through human skin

The purpose of this study was to investigate the effects of ethosomes, chemical enhancers and their binary combination on the in vitro permeability enhancement of naloxone through human skin. Franz diffusion cells were used for the percutaneous absorption studies. Propylene glycol (PG), N,N-dimethyl formamide (N,N-DMF), N,N-dimethyl acetamide (N,N-DMA), dimethyl sulfoxide (DMSO), Azone and polyethylene glycol 400 (PEG400), were chosen as the chemical enhancers. Naloxone ethosomes showed 11.68 times increase in steady-state flux compared to phosphate buffered solution (PBS). Ethosomes in combination with chemical enhancers synergistically increased (p < 0.05) in vitro flux of naloxone. Azone 3% + PG7% pretreated in ethosomal form dramatically enhanced the skin permeation of naloxone in vitro compared with ethosomes (steady-state flux: 96.75 +/- 5.70 microg x cm(-2) x h(-1) vs 20.56 +/- 1.67 microg x cm(-2) x h(-1)). Ethosomal carrier and enhancers accumulated in the skin after 24 h were greater than that of PBS.