title: 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 =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.
authors.affiliation: College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi, Republic of Korea.
authors.forename: Alam
authors.initials: A
authors.lastname: Zeb
authors.affiliation: College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi, Republic of Korea.
authors.forename: Omer Salman
authors.initials: OS
authors.lastname: Qureshi
authors.affiliation: College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi, Republic of Korea.
authors.forename: Hyung-Seo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi, Republic of Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Cha
authors.affiliation: College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi, Republic of Korea.
authors.forename: Hoo-Seong
authors.initials: HS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi, Republic of Korea.
authors.forename: Jin-Ki
authors.initials: JK
authors.lastname: Kim
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000737:chemistry; D018613:Microscopy, Confocal; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D011136:Polysorbates; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects*; D012869:Skin Absorption / Q000187:drug effects; D020358:Sodium Cholate / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D010713:Phosphatidylcholines; D011136:Polysorbates; D020358:Sodium Cholate; D008727:Methotrexate
keywords: deformability; methotrexate; skin permeation; transdermal delivery; ultradeformable liposomes