Shinoda Shotaro, Tanigawa Mina, Sakuragi Mina
Faculty of Engineering, Department of Nanoscience, Sojo University 4-22-1 Ikeda, Nishi-ku Kumamoto City 860-0082 Japan
RSC Adv. 2025 Mar 24;15(12):8977-8985. doi: 10.1039/d5ra00403a. eCollection 2025 Mar 21.
Deep eutectic solvents (DESs) can enhance the penetration of drug carriers in transdermal drug delivery systems. Previously, we showed that terpene-based DESs substantially enhance the penetration of drug carriers but cause skin damage. To retain the penetration-enhancing properties of DESs while mitigating their adverse effects on the skin, we incorporated small amounts of terpene-based DESs into the oil phase, formulating water-in-oil-type microemulsions (MEs). Stratum corneum (SC) lipid layers, which are sensitive to hydration levels, exhibit changes in spacing and regularity when interacting with DESs. Furthermore, DESs disrupt the lipid structure unique mechanisms differing from those of traditional MEs. Herein, we investigated the effect of DES concentrations in the MEs on skin permeation under different hydration conditions. Utilizing synchrotron small-angle X-ray scattering and small-angle neutron scattering methods, we analyzed the molecular-scale interactions between the MEs and SC lipids to effectively understand their interaction behavior across hydration states. Overall, these findings highlight the importance of optimizing DES contents and SC hydration levels to achieve an efficient and safe transdermal drug delivery system.
深共熔溶剂（DESs）可增强药物载体在透皮给药系统中的渗透。此前，我们发现基于萜烯的DESs能显著增强药物载体的渗透，但会导致皮肤损伤。为了保留DESs的促渗透特性，同时减轻其对皮肤的不良影响，我们将少量基于萜烯的DESs加入油相中，制备了油包水型微乳（MEs）。对角质层（SC）脂质层而言，其对水合水平敏感，与DESs相互作用时会表现出间距和规则性的变化。此外，DESs破坏脂质结构的机制与传统MEs不同。在此，我们研究了不同水合条件下MEs中DES浓度对皮肤渗透的影响。利用同步辐射小角X射线散射和小角中子散射方法，我们分析了MEs与SC脂质之间的分子尺度相互作用，以有效了解它们在不同水合状态下的相互作用行为。总体而言，这些发现凸显了优化DES含量和SC水合水平对于实现高效安全的透皮给药系统的重要性。
