Department of Applied Chemistry, Graduate School of Engineering, Kyushu University, Fukuoka, Japan.
Eur J Pharm Biopharm. 2012 Sep;82(1):158-63. doi: 10.1016/j.ejpb.2012.05.016. Epub 2012 Jun 17.
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).
采用固-油（S/O）技术研究了甲氨蝶呤（MTX）的透皮给药。由于 MTX 被非离子表面活性剂分子包裹，所得复合物易溶于各种有机溶剂，并在肉豆蔻异丙酯（IPM）中提供透明溶液。通过添加碱性氨基酸（如 L-精氨酸（L-Arg）或 L-赖氨酸（L-Lys）），可以增强 MTX-表面活性剂复合物的稳定性。MTX 和氨基酸的分散复合物的平均粒径减小至 100nm 以下，并呈现均匀分布。使用 S/O 纳米载体进行了透皮给药实验，并使用 Franz 扩散池评估了 MTX 通过 Yucatan 微型猪（YMP）皮肤的渗透行为。与对照水溶液相比，S/O 纳米载体（未添加尿素）的渗透效率增加了两到三倍，因为基于油的纳米载体对于穿透角质层是有效的。此外，尿素的添加大大改善了 MTX 从 S/O 纳米载体中的释放性能，并且在 24 小时后，含有尿素的 S/O 纳米载体的渗透效率最佳，与对照水溶液相比增加了约 8.8 倍（p<0.01）。
