Application of vesicles to rat skin in vivo: a confocal laser scanning microscopy study.
A major problem in (trans)dermal drug delivery is the low penetration rate of most substances through the barrier of the skin, the stratum corneum. One of the methods to increase the penetration rate across the skin is encapsulation of a (model) drug in lipid vesicles. In this study fluorescently labelled liposomes were applied on rat skin, in vivo. Bilayer labelled gel-state and liquid-state liposomes (conventional or with flexible bilayers) were non-occlusively applied on the dorsal area in the neck of the rat for 1, 3 or 6 h. Micelles were used as a control formulation. The penetration pathway and penetration depth of the lipophilic fluorescent label into the skin was visualised by confocal laser scanning microscopy (CLSM). During the first 3 h of application almost no differences in penetration depth were observed, when the label was applied in the various formulations. After 6 h application, it was clear that the label applied in micelles and gel-state liposomes did not penetrate as deep into the skin as the label applied in liquid-state vesicles. Among the liquid-state vesicles, the suspension with the most flexible bilayers showed the highest fluorescence intensity in the viable epidermis and dermis, 6 h post-application. Thus the vesicular form and the thermodynamic state of the bilayer and to a smaller extent the flexibility of the bilayer influence the penetration depth of the label into the skin at longer application periods. These results are in good agreement with CLSM results obtained from in vitro experiments with human skin.
van Kuijk-Meuwissen
M E
ME
Division of Pharmaceutical Technology, Leiden/Amsterdam Center of Drug Research (LACDR), Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
Mougin
L
L
Junginger
H E
HE
Bouwstra
J A
JA
D000279:Administration, Cutaneous; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D005782:Gels; D008051:Lipid Bilayers / Q000378:metabolism; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008823:Micelles; D018613:Microscopy, Confocal / Q000379:methods; D010743:Phospholipids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000033:anatomy & histology / Q000378:metabolism; D012869:Skin Absorption; D013816:Thermodynamics
D005456:Fluorescent Dyes; D005782:Gels; D008051:Lipid Bilayers; D008081:Liposomes; D008823:Micelles; D010743:Phospholipids