Liposomes as a topical delivery system: the role of size on transport studied by the EPR imaging method.

The relative contribution of the liposome size, lamellarity, composition and charge to the transport into the skin of drug, which was applied entrapped in liposomes is a subject of some controversy. In this study the influence of liposome size on the transport of hydrophilic substance was investigated. For this purpose liposomes composed of dipalmitoylphosphatidylcholine (DPPC), or non-hydrogenated soya lecithin (NSL) or hydrogenated soya lecithin (HSL), all in combination with 30% cholesterol, as well as of two types of niosomes: from glyceryl distearate or PEG stearate in combination with 45% of cholesterol and 10% of lipoaminosalt were prepared and their physical characteristics (size, polydispersity index, zeta potential, entrapped volume) were determined. Their size was varied by extrusion and by sonication. The transport of the entrapped spin labeled hydrophilic compounds into the skin was measured by electron paramagnetic resonance imaging methods. No significant transport into the deeper skin layers (more than 100 microm deep) was observed for NSL liposomes, irrespective of vesicle size. For all other vesicular systems some transport into the deeper skin layers was observed, which did not depend on vesicle size, significantly until the vesicle diameter of approximately 200 nm was reached. However, for small vesicles (with diameter less than 200 nm) the transport is significantly decreased. We have proven that small vesicles are not stable and disintegrate immediately in contact with other surfaces. As a consequence, they lose an important influence on the topical delivery of the entrapped hydrophilic substances.

Influence of liposome bilayer fluidity on the transport of encapsulated substance into the skin as evaluated by EPR.

PURPOSE: The influence of liposome composition on the bilayer fluidity and on the transport of encapsulated substance into the skin was investigated. METHODS: Multilamellar vesicles (MLV) from dipalmitoylphosphatidylcholine (DPPC) or dimyristoylphosphatidylcholine (DMPC) with various amounts of cholesterol were prepared by the film method and characterised by photon correlation spectroscopy and electron paramagnetic resonance (EPR) methods. The transport of the hydrophilic spin probe encapsulated in MLV into pig ear skin was investigated by EPR imaging methods. The bilayer domain structure was studied by fitting the lineshape of the experimental EPR spectra with the spectra calculated by the model, which takes into account the heterogeneous structure of the bilayer with several coexisting domains. RESULTS: Cholesterol strongly influences the entrapped volume of liposomes, the domain structure of the lipid bilayer, and the transport of hydrophilic spin probe into the skin. Transport was not observed for liposomes composed of phospholipid:cholesterol 1:0 or 9:1 (mol:mol), not even above the phase transition temperature from the gel to the liquid crystalline phase of DMPC. A significant delivery of hydrophilic spin probe was observed only if there was 30 or 50 mol% of cholesterol in the liposome bilayer. CONCLUSIONS: It can be concluded that the domain structure of the liposome bilayer is more important for the delivery of encapsulated substance into the skin than the liquid crystalline phase of the pure phospholipids bilayer.