Transdermal delivery of the anti-rheumatic agent methotrexate using a solid-in-oil nanocarrier.
Transdermal delivery of methotrexate (MTX) was investigated by using the solid-in-oil (S/O) technique. Because MTX was coated with nonionic surfactant molecules, the resulting complex was easy to dissolve in various organic solvents and provided a transparent solution in isopropyl myristate (IPM). The stability of MTX-surfactant complexes are enhanced by the addition of a basic amino acid such as L-Arginine (L-Arg) or L-Lysine (L-Lys). The average size of the dispersed complex of MTX and amino acid was reduced to below 100 nm and gave a uniform distribution. A transdermal delivery experiment was conducted using the S/O nanocarrier, and the permeation behavior of MTX through Yucatan micropig (YMP) skin was evaluated with a Franz diffusion cell. The permeation efficiency for the S/O nanocarrier (not urea addition) was two- to threefold increased compared to that of the control aqueous solution because the oil-based nanocarrier is effective for penetrating the stratum corneum. Furthermore, addition of urea has dramatically improved the release property of MTX from the S/O nanocarrier, and the S/O nanocarrier containing urea showed an optimal permeation efficiency of approximately 8.8-fold increased compared to that of the control aqueous solution after 24h (p<0.01).
Department of Applied Chemistry, Graduate School of Engineering, Kyushu University, Fukuoka, Japan.
Fan
F
Yang
Noriho
N
Kamiya
Masahiro
M
Goto
D000279:Administration, Cutaneous; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004355:Drug Stability; D005260:Female; D008727:Methotrexate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009226:Myristates / Q000737:chemistry; D049329:Nanostructures; D010316:Particle Size; D010539:Permeability; D012869:Skin Absorption; D012997:Solvents / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry; D013552:Swine; D013556:Swine, Miniature; D014508:Urea / Q000737:chemistry
D000596:Amino Acids; D018501:Antirheumatic Agents; D004337:Drug Carriers; D009226:Myristates; D012997:Solvents; D013501:Surface-Active Agents; C008205:isopropyl myristate; D014508:Urea; D008727:Methotrexate