Improved skin permeation of methotrexate via nanosized ultradeformable liposomes

• Published in: International journal of nanomedicine Vol. 11; pp. 3813 - 3824
• Main Authors: Zeb, Alam, Qureshi, Omer Salman, Kim, Hyung-Seo, Cha, Ji-Hye, Kim, Hoo-Seong, Kim, Jin-Ki
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2016; Taylor & Francis Ltd; Dove Medical Press
• Subjects: Administration, Cutaneous; Animals; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug delivery systems; Drug Delivery Systems - methods; Investigations; Lipids; Liposomes - administration & dosage; Liposomes - chemistry; Male; Methotrexate; Methotrexate - administration & dosage; Methotrexate - chemistry; Microscopy, Confocal; Nanostructures - administration & dosage; Nanostructures - chemistry; Original Research; Particle Size; Phosphatidylcholines - chemistry; Polysorbates; Rats, Sprague-Dawley; Skin; Skin - drug effects; Skin Absorption - drug effects; Sodium Cholate - chemistry; Transdermal medication; United States > US; skin permeation; methotrexate; deformability; ultradeformable liposomes; transdermal delivery
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S109565

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 =7:3, 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.