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 24 h (p < 0.01).

Graphical abstractAn oil-based nanocarrier promotes the penetration of drugs through the high-lipophilic stratum corneum.Figure optionsDownload full-size imageDownload high-quality image (88 K)Download as PowerPoint slideHighlights► Transdermal delivery of methotrexate (MTX) with basic amino acids was explored. ► The solid-in-oil (S/O) nanocarrier including MTX and Arg or Lys was prepared. ► The average size of the S/O nanocarrier in isopropyl myristate was below 100 nm. ► The oil-based nanocarrier effectively penetrated into the stratum corneum. ► Addition of urea improved the release property of MTX from the S/O nanocarrier.