Abstract
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 100nm 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).
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