Improved skin permeation of methotrexate via nanosized ultradeformable liposomes.

ABSTRACT

The aim of this study is to investigate methotrexate-entrapped ultradeformable liposomes (MTX-UDLs) for potential transdermal application. MTX-UDLs were prepared by extrusion method with phosphatidylcholine as a bilayer matrix and sodium cholate or Tween 80 as an edge activator. The physicochemical properties of MTX-UDLs were determined in terms of particle size, polydispersity index, zeta potential, and entrapment efficiency. The deformability of MTX-UDLs was compared with that of methotrexate-entrapped conventional liposomes (MTX-CLs) using a steel pressure filter device. The skin permeation of MTX-UDLs was investigated using Franz diffusion cell, and the skin penetration depth of rhodamine 6G-entrapped UDLs was determined by confocal laser scanning microscopy. MTX-UDLs showed a narrow size distribution, with the particle size of ~100 nm. The deformability of MTX-UDLs was two to five times greater than that of MTX-CLs. The skin permeation of MTX-UDLs was significantly improved compared with MTX-CLs and free MTX solution. The optimized UDLs (phosphatidylcholine Tween 80 =73, w/w) showed a higher fluorescence intensity than conventional liposomes at every increment of skin depth. Thus, the optimized UDLs could be promising nanocarriers for systemic delivery of MTX across skin.