Okada Akie, Niki Rina, Inoue Yutaka, Tomita Junki, Todo Hiroaki, Itakura Shoko, Sugibayashi Kenji
Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado 350-0295, Saitama, Japan.
Research Analysis Center, Josai University, 1-1 Keyakidai, Sakado 350-0295, Saitama, Japan.
Pharmaceutics. 2022 Apr 3;14(4):785. doi: 10.3390/pharmaceutics14040785.
In recent years, the development of self-injectable formulations has attracted much attention, and the development of formulations to control pharmacokinetics, as well as drug release and migration in the skin, has become an active research area. In the present study, the development of a lipid-based depot formulation containing leuprorelin acetate (LA) as an easily metabolizable drug in the skin was prepared with a novel non-lamellar liquid-crystal-forming lipid of mono--(5,9,13-trimethyl-4-tetradecenyl) glycerol ester (MGE). Small-angle X-ray scattering, cryo-transmission electron microscopy, and nuclear magnetic resonance observations showed that the MGE-containing formulations had a face-centered cubic packed micellar structure. In addition, the bioavailability () of LA after subcutaneous injection was significantly improved with the MGE-containing formulation compared with the administration of LA solution. Notably, higher and faster were obtained with the MGE-containing formulation, and the increased with increasing MGE content in the formulation, suggesting that LA migration into the systemic circulation and its stability might be enhanced by MGE. These results may support the development of self-administered formulations of peptide drugs as well as nucleic acids, which are easily metabolized in the skin.
近年来，可自我注射制剂的开发备受关注，控制药代动力学以及药物在皮肤中的释放和迁移的制剂开发已成为一个活跃的研究领域。在本研究中，以单 -（5,9,13 - 三甲基 - 4 - 十四碳烯基）甘油酯（MGE）这种新型非层状液晶形成脂质制备了含有醋酸亮丙瑞林（LA）的脂质型长效制剂，LA是一种在皮肤中易代谢的药物。小角X射线散射、冷冻透射电子显微镜和核磁共振观察表明，含MGE的制剂具有面心立方堆积胶束结构。此外，与注射LA溶液相比，含MGE的制剂皮下注射后LA的生物利用度（）显著提高。值得注意的是，含MGE的制剂获得了更高且更快的（此处原文可能有误，推测是生物利用度相关参数），并且随着制剂中MGE含量的增加而增加，这表明MGE可能增强了LA向体循环的迁移及其稳定性。这些结果可能支持肽类药物以及在皮肤中易代谢的核酸的自我给药制剂的开发。
