The effects of pH and ionic strength on topical delivery of a negatively charged porphyrin (TPPS4)

Meso-tetra-[4-sulfonatophenyl]-porphyrin (TPPS4) is a charged porphyrin derivate used in photodynamic therapy (PDT) by parenteral administration. This study means to investigate potential enhancement for its topical delivery by determining the TPPS4 dependence on the environmental characteristics and applying iontophoresis. In order to accomplish this task, cathodal and anodal iontophoresis as well as passive delivery of the drug were studied in vitro and in vivo in function of its concentration, pH and ionic strength. A reduction in drug concentration as well as the NaCl elimination from donor formulation at pH 2.0 increased TPPS4 passive permeation through the skin in vitro. Iontophoresis improved TPPS4 delivery across the skin when applied in solutions containing NaCl at pH 2.0, regardless electrode polarity. However, at pH 7.4, the amount of TPPS4 permeated by iontophoresis was not different from that one permeated after passive experiments from a solution containing NaCl. Despite the fact that iontophoresis did not improve TPPS4 transdermal delivery at this specific condition, in vivo experiments showed that 10 min of iontophoresis quickly and homogeneously delivered TPPS4 to deeper skin layers when compared to passive administration, which is an important condition for topical treatment of skin tumors with PDT. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association.