The Effects of Calcium Chloride and Sodium Chloride on the Electroporation-Mediated Skin Permeation of Fluorescein Isothiocyanate (FITC)-Dextrans in Vitro

We previously reported the substantial synergic effects of electroporation and electrolytes, particularly those containing CaCl2 on the skin permeation of the model low-molecular weight compound, calcein. We then investigated the effects of electroporation (300 V, 10 ms×10 times) and 150 mM NaCl or CaCl2 on skin permeation of higher molecular weight compounds, fluorescein isothiocyanate (FITC)-dextrans (FD-4, FD-10 and FD-40; average molecular weight, 4.4, 9.6 and 35.6 kDa, respectively) using excised hairless rat skin. The observed steady state flux of FD-4 was 1.3 pmol/cm2/h after electroporation without NaCl or CaCl2. The flux did not differ greatly from that without electroporation. In contrast, a much higher steady state flux was observed after electroporation with NaCl or CaCl2 (2.5 and 8.2 pmol/cm2/h, respectively). For FD-10 and FD-40, no flux was detected with electroporation in water (without electrolytes) or without electroporation. On the other hand, high skin permeation was observed after electroporation in NaCl or CaCl2 solution (FD-10: 7.5 and 18.2 pmol/cm2/h, FD-40: 4.5 and 9.3 pmol/cm2/h in NaCl and CaCl2, respectively). The effects of CaCl2 on FD permeation were greater than those of NaCl. The present finding suggests that electroporation application in the presence of electrolytes, particularly CaCl2, was very effective in increasing transdermal delivery of water-soluble macromolecules.