The synergic effects of various electrolytes and electroporation on the in vitro skin permeation of calcein.

Various electrolytes in test solutions applied to the skin were evaluated with regard to their effects on enhanced skin permeation of calcein as a model permeant by electroporation (EP), which is a physical means to increase skin penetration by applying a high voltage pulse on the skin surface. Calcein solution (1.0 mM) containing different electrolytes at a concentration of 150 mM was applied to excised hairless rat skin, and a 10-ms electric pulse of 300 V was applied to the skin surface ten times (one pulse every second) at the beginning of the in vitro permeation experiments. The following results were obtained: (i) addition of several electrolytes, such as CaCl2 and NaCl, further increased the EP-enhanced skin permeation of calcein when compared to treatment without these electrolytes; (ii) Ca2+ and Mg2+ exerted a greater effect than other cations (Na+, Zn2+, Cu2+, Fe3+ and Al3+); (iii) with simultaneous application of CaCl2 and EP, the effect of anodal EP was much greater than that of cathodal EP; (iv) the penetration-enhancing effects of CaCl2 were also obtained with EP pretreatment followed by calcein addition; and (v) skin permeation was greatly increased particularly with simultaneous application of EP and Ca2+. These substantial combined synergic effects of EP and electrolytes, particularly those containing CaCl2, MgCl2 and CaBr2, may be related to the disruptive and retrievable functions of the biggest barrier of skin, the stratum corneum, of these electrolytes.