Interaction of liposomes with human skin in vitro--the influence of lipid composition and structure.
Liposomes have been suggested as a vehicle for dermal and transdermal drug delivery, but the knowledge about the interaction between lipid vesicles and human skin is poor. Therefore, we visualized liposome penetration into the human skin by confocal laser scanning microscopy (CLSM) in vitro. Liposomes were prepared from phospholipids in different compositions and labeled with a fluorescent lipid bilayer marker, N-Rh-PE (L-alpha-phosphatidylethanolamine-N-lissamine rhodamine B sulfonyl). Fluorescently labelled liposomes were not able to penetrate into the granular layers of epidermis. However, the fluorescence from liposome compositions containing DOPE (dioleylphosphatidyl ethanolamine) was able to penetrate deeper into the stratum corneum than that from liposomes without DOPE. Pretreatment of skin with unlabeled liposomes containing DOPE or lyso-phosphatidyl choline (lyso-PC) enhanced the subsequent penetration of the fluorescent markers, N-Rh-PE and sulforhodamine B into the skin, suggesting possible enhancer activity, while most liposomes did not show such enhancement. Resonance energy transfer (RET) and calcein release assay between stratum corneum lipid liposomes (SCLLs) and the phospholipid vesicles suggested that the liposomes containing DOPE may fuse or mix with skin lipids in vitro and loosen the SCLL bilayers, respectively. Among the factors not affecting stratum corneum penetration were: negative charge, cholesterol inclusion and acyl chain length of the phospholipids. In conclusion, fusogenicity of the liposome composition appears to be a prerequisite for the skin penetration.
Kirjavainen
M
M
Department of Pharmaceutics, University of Kuopio, Finland.
Urtti
A
A
Jääskeläinen
I
I
Suhonen
T M
TM
Paronen
P
P
Valjakka-Koskela
R
R
Kiesvaara
J
J
Mönkkönen
J
J
D004337:Drug Carriers; D005452:Fluoresceins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D005470:Fluorometry; D006801:Humans; D050356:Lipid Metabolism; D008081:Liposomes / Q000378:metabolism*; D008561:Membrane Fusion; D018613:Microscopy, Confocal; D010316:Particle Size; D010539:Permeability; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D012235:Rhodamines / Q000378:metabolism; D012867:Skin / Q000378:metabolism*
D004337:Drug Carriers; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008081:Liposomes; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D012235:Rhodamines; C046703:lissamine-rhodamine-phosphatidylethanolamine; C007740:fluorexon