Influence of various penetration enhancers on the in vitro permeation of amino acids across hairless mouse skin

Abstract

The influence of various penetration enhancers including propylene glycol, oleic acid, Azone ®, isopropyl myristate, valine, and nanoparticles on the permeation coefficient for the permeation of amino acids through hairless mouse skin as well as a dialysis membrane was assessed in vitro. The two different types of membranes were employed in order to distinguish between effects due to thermodynamic parameters and those due to barrier resistance. Furthermore, the influence of these penetration enhancers on the amount of amino acids remaining within the skin was determined. Oleic acid was found to be the most efficient enhancer for amino acids (enhancement factor (EF) of 176 for histidine) followed by Azone ® (EF of 45 for phenylalanine). All other penetration enhancers failed to exert any significant effect on the skin permeation of amino acids. The fact that the enhancement effects of oleic acid and Azone ® are not reversible and that the enhancers exhibited no influence with dialysis membranes clearly indicate that both penetration enhancers induce their effects on the basis of changes in skin morphology. Choosing arginine, histidine and phenylalanine as test permeants enabled a correlation between the enhancement effects and the degree of ionization of the test permeant. Histidine is the only amino acid which is unionized at pH 7.4 due to its isoelectric point. This might be the reason why the permeation enhancement induced by valine was only detectable with histidine, and not with the other two amino acids. Neither penetration enhancer resulted in any significant effect on the amount of the amino acid accumulated in the skin.