Enhanced transfollicular delivery of adriamycin with a liposome and iontophoresis.

To find a better way to deliver drugs into hair follicles, we tried two approaches: single topical application using various liposomes; and iontophoresis combined with topical application of ionic liposome. After delivery of adriamycin (ADR) to wax-depilated rat skin, the transport of the drug was examined under fluorescence microscopy. Most liposomal ADR showed more effective transdermal and transfollicular penetration than free ADR. Among tested liposomes, the non-ionic GDL liposome (GDL/CH/POE-10 = glycerol dilaulate/cholesterol/polyoxyethylene-10) was the most selective to hair follicles against skin, while the cationic liposome (GDL/CH/POE-10/DOTAP, dioleoyl trimethylammonium propane) containing monocationic DOTAP was less selective; however, it was better at improving the delivery amount and penetration of ADR into the follicles and skin. The DMPC/DMPG (7/3) formulation of anionic PC liposome (DMPC/DMPG = dimyristoyl-phosphocholine/-phospoglycerol) showed results similar to the cationic liposome. The DMPC/DMPG (3/7) formulation yielded poor results, however, probably because of its increased viscosity and anionic property. Although ADR delivery was enhanced by liposomal formulations, topical applications had some limitations in delivery capacity and speed. To accelerate delivery, iontophoresis was combined with the cationic liposome at positive 0.2-0.4 mA/cm(2) for 20-30 min. The resulting delivery of ADR through follicular routes was excellent. This combination method diffused ADR 3.0-fold more efficiently, rapidly and deeply than single topical application of cationic liposomal ADR. This system also achieved a 3.5-fold higher diffusive follicular delivery than a free ADR/iontophoresis combination. Furthermore, it was demonstrated that the tetracationic lipid DOSPER and hydrophile spermine could serve as a cationic additive instead of the monocationic DOTAP in the liposome. These results suggest that the combinative system of the topically applied cationic liposome followed by iontophoresis has a significant synergistic effect on the transfollicular delivery of ADR.