Abstract

This study attempted to identify a good selection method for phospholipids to design liposome preparations with high skin penetration-enhancing effects. Five kinds of phosphatidylcholines and phosphatidylglycerols each were selected. First, phospholipid aqueous dispersions and liposomes containing caffeine as a model drug were tested for their skin penetration-enhancing effects using excised hairless rat skin. Accordingly, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol, sodium salt (DPPG) dispersions showed high penetration-enhancing ratios (ERs), whereas DPPG, 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC), and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes showed high ERs, suggesting that liposomes had different skin penetration-enhancing mechanisms from phospholipid dispersions. Next, two experiments were done to clarify the possible mechanism of liposome penetration; excised skin was pretreated for 1 h with caffeine-free phospholipid dispersions and liposomes, and caffeine solution was added to determine its skin permeation. Separately, caffeine permeation experiments were done using physical mixtures of blank liposomes and caffeine solution (caffeine-spiked liposomes) and caffeine-entrapped liposomes (caffeine was entrapped only in liposomes). DPPG was found to be a promising phospholipid candidate for liposome formulations with high skin penetration-enhancing effects, because DPPG phospholipid and liposome vesicles had a combination effect of disrupting the SC lipid barrier to carry both free and entrapped caffeine in the formulation through the skin.