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 CaCl(2) on the skin permeation of the model low-molecular weight compound, calcein. We then investigated the effects of electroporation (300 V, 10 msx10 times) and 150 mM NaCl or CaCl(2) 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/cm(2)/h after electroporation without NaCl or CaCl(2). 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 CaCl(2) (2.5 and 8.2 pmol/cm(2)/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 CaCl(2) solution (FD-10: 7.5 and 18.2 pmol/cm(2)/h, FD-40: 4.5 and 9.3 pmol/cm(2)/h in NaCl and CaCl(2), respectively). The effects of CaCl(2) on FD permeation were greater than those of NaCl. The present finding suggests that electroporation application in the presence of electrolytes, particularly CaCl(2), was very effective in increasing transdermal delivery of water-soluble macromolecules.
Tokudome
Yoshihiro
Y
Faculty of Pharmaceutical Sciences, Josai University, Japan.
Sugibayashi
Kenji
K
D000818:Animals; D002122:Calcium Chloride / Q000493:pharmacokinetics*; D003911:Dextrans / Q000493:pharmacokinetics; D004357:Drug Synergism; D018274:Electroporation / Q000379:methods*; D016650:Fluorescein-5-isothiocyanate / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology*; D012965:Sodium Chloride / Q000493:pharmacokinetics*
D003911:Dextrans; D012965:Sodium Chloride; D016650:Fluorescein-5-isothiocyanate; D002122:Calcium Chloride