Effect of positively and negatively charged liposomes on skin permeation of drugs

To clarify the effect of the surface charge of liposomes on percutaneous ab sorption, the permeation of liposomal drugs through rat skin was investigat ed in vitro and in vivo. Liposomes were prepared using egg yolk lecithin (E PC, phase transition temperature, -15 to -17 degreesC), cholesterol and dic etylphosphate (DP) or stearylamine (SA) (10:1:1, mol/mol). Also examined wa s the penetration behavior of positively and negatively charged liposomes, using a fluorescent probe (Nile Red). The in vitro penetration rate of mela tonin (MT) entrapped in negatively charged liposomes was higher than that o f positively charged ones (p<0.05). When the percutaneous absorption of eth osuximide (ES) encapsulated was estimated in vivo, the absorption of ES fro m negatively charged liposomes was slightly higher than that from positivel y charged liposomes. Additionally, the absorption of ES from both types of liposomes was superior to that from the lipid mixtures consisting of the sa me composition as the vesicles. The percutaneous absorption of betahistine (BH) from a gel formulation containing negatively charged liposomes of BH w as much more than that from the formulation with positively charged ones, w ith 2-fold higher AUC (p<0.05), Histological studies revealed that the nega tively charged liposomes diffused to the dermis and the lower portion of ha ir follicles through the stratum corneum and the follicles much faster than the positive vesicles at the intitial time stage after application. Thus, the rapid penetration of negatively charged liposomes would contribute to t he increased permeation of drugs through the skin.