Effect of positively and negatively charged liposomes on skin permeation of drugs.
To clarify the effect of the surface charge of liposomes on percutaneous absorption, the permeation of liposomal drugs through rat skin was investigated in vitro and in vivo. Liposomes were prepared using egg yolk lecithin (EPC, phase transition temperature, -15 to -17 degrees C), cholesterol and dicetylphosphate (DP) or stearylamine (SA) (10:1:1, mol/mol). Also examined was the penetration behavior of positively and negatively charged liposomes, using a fluorescent probe (Nile Red). The in vitro penetration rate of melatonin (MT) entrapped in negatively charged liposomes was higher than that of positively charged ones (p<0.05). When the percutaneous absorption of ethosuximide (ES) encapsulated was estimated in vivo, the absorption of ES from negatively charged liposomes was slightly higher than that from positively charged liposomes. Additionally, the absorption of ES from both types of liposomes was superior to that from the lipid mixtures consisting of the same composition as the vesicles. The percutaneous absorption of betahistine (BH) from a gel formulation containing negatively charged liposomes of BH was much more than that from the formulation with positively charged ones, with 2-fold higher AUC (p<0.05). Histological studies revealed that the negatively charged liposomes diffused to the dermis and the lower portion of hair follicles through the stratum corneum and the follicles much faster than the positive vesicles at the initial time stage after application. Thus, the rapid penetration of negatively charged liposomes would contribute to the increased permeation of drugs through the skin.
Ogiso
T
T
Faculty of Pharmaceutical Sciences, Kinki University, Kowakae 3-4-1, Higashi-Osaka, Osaka 577-8502, Japan.
Yamaguchi
T
T
Iwaki
M
M
Tanino
T
T
Miyake
Y
Y
D000279:Administration, Cutaneous; D000818:Animals; D019540:Area Under Curve; D001621:Betahistine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D016503:Drug Delivery Systems; D005013:Ethosuximide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007124:Immunoenzyme Techniques; D008081:Liposomes; D008550:Melatonin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008560:Membrane Fluidity; D008856:Microscopy, Fluorescence; D051381:Rats; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D012869:Skin Absorption
D008081:Liposomes; D005013:Ethosuximide; D008550:Melatonin; D001621:Betahistine