Gao Wenyan, Xing Wenmin, Tang Zhan, Wang Qiao, Yu Wenying, Zhang Qi
School of Pharmacy, Hangzhou Medical College, Hangzhou, China.
Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, Hangzhou Medical College, Hangzhou, China.
Drug Deliv. 2025 Dec;32(1):2489730. doi: 10.1080/10717544.2025.2489730. Epub 2025 Apr 21.
Low solubility restricted transdermal penetration of drugs. We aimed to develop a novel ionic liquid-iontophoresis (IL-IS) technology and assess their efficacy and primary factors in facilitating transdermal drug delivery. Five choline-based ILs with different chain length were synthesized and validated, and the impact of IL and/or IS technology on transdermal penetration of model drugs were investigated. The results indicated that five groups of ILs synthesized in this study exhibited minimal level of toxicity, and the longer the chain of acid ligands of ILs, the greater the cytotoxicity. The longer chain of acid ligand was demonstrated superior solubilizing capabilities compared to the shorter chain. Cinnamic acid-choline-based IL ([Cho] [Cin]) significantly improved permeation of all three model drugs, and permeation quantity was linearly positively associated with the concentration of ILs. The 10 h cumulative permeation of aripiprazole applied with ILs alone was enhanced by about 14-fold when paired with IS, and the penetration was linearly positively associated with the concentration and current strength of the ILs. results indicated that IL and/or IS technology primarily facilitated drug penetration into the skin, with potential involvement of endocytosis in this process. This study demonstrated that [Cho] [Cin] exhibited a significant enhancement in the transdermal delivery of three sparingly soluble drugs. It further enhanced the transdermal permeation of weak base drug following with the combining IL and IS technology. These findings highlighted that the IL-IS technology holded promise for facilitating the transdermal delivery of sparingly soluble and weak base drugs.
药物的低溶解度限制了其经皮渗透。我们旨在开发一种新型离子液体-离子电渗疗法（IL-IS）技术，并评估其在促进药物经皮递送中的疗效及主要影响因素。合成并验证了五种不同链长的胆碱基离子液体，研究了离子液体和/或离子电渗疗法技术对模型药物经皮渗透的影响。结果表明，本研究合成的五组离子液体表现出最低程度的毒性，且离子液体酸性配体的链越长，细胞毒性越大。与较短链相比，较长链的酸性配体表现出更强的增溶能力。肉桂酸-胆碱基离子液体（[Cho][Cin]）显著提高了所有三种模型药物的渗透，且渗透量与离子液体浓度呈线性正相关。单独使用离子液体时阿立哌唑的10小时累积渗透量，在与离子电渗疗法结合后提高了约14倍，且渗透与离子液体的浓度和电流强度呈线性正相关。结果表明，离子液体和/或离子电渗疗法技术主要促进了药物渗透进入皮肤，此过程中可能涉及内吞作用。本研究表明，[Cho][Cin]在三种难溶性药物的经皮递送方面表现出显著增强作用。离子液体与离子电渗疗法技术联合使用进一步增强了弱碱性药物的经皮渗透。这些发现突出表明，离子液体-离子电渗疗法技术在促进难溶性和弱碱性药物经皮递送方面具有前景。
