Enhanced transdermal transport by electroporation using anionic lipids.

Transdermal drug delivery is an attractive approach for either local or systemic treatment in medicine. In the last decade, different active transdermal delivery methods have been further investigated such as cationic liposomal delivery and electroporation-enhanced delivery. In light of gaining a synergistic effect of lipid and electroporation, a new method of using anionic lipids to enhance the transdermal transport of molecules under electroporation is reported here. Heat-stripped porcine epidermis was used for measurement of transdermal transport using an in vitro vertical diffusion apparatus. Lipid vesicles were prepared using a 1:1 mole ratio mixture of 1,2-dioleoyl-3-phosphatidylglycerol (DOPG) and 1,2-dioleoyl-3-phosphatidylcholine (DOPC). When the lipids were mixed with (but not encapsulating) the transport target molecule, the electroporation-induced transport through porcine epidermis was increased as compared to that without the lipids. The enhancement in transport was dependent upon the size and the charge of the transported molecule. Methylene blue (MB), protoporphyrin IX (PpIX) and dimethyl-protoporphyrin IX (DM-PpIX) were used as small target molecules, and FITC-dextrans (4 to 155 kDa) were used as large target molecules in our studies. Enhancement of transport, to varying degree, was observed for all three small molecules (molecular weights <1 kDa), in the presence of DOPG:DOPC vesicles. In the case of large molecules, lipid-enhanced transport was only observed for the 4 kDa dextran, and not for the larger ones (M(w)>10 kDa). Neutral or cationic lipids alone did not enhance the transdermal transport under the electroporation conditions we used.