School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
J Nanobiotechnology. 2024 May 21;22(1):272. doi: 10.1186/s12951-024-02552-y.
Transdermal delivery of sparingly soluble drugs is challenging due to their low solubility and poor permeability. Deep eutectic solvent (DES)/or ionic liquid (IL)-mediated nanocarriers are attracting increasing attention. However, most of them require the addition of auxiliary materials (such as surfactants or organic solvents) to maintain the stability of formulations, which may cause skin irritation and potential toxicity.
We fabricated an amphiphilic DES using natural oxymatrine and lauric acid and constructed a novel self-assembled reverse nanomicelle system (DES-RM) based on the features of this DES. Synthesized DESs showed the broad liquid window and significantly solubilized a series of sparingly soluble drugs, and quantitative structure-activity relationship (QSAR) models with good prediction ability were further built. The experimental and molecular dynamics simulation elucidated that the self-assembly of DES-RM was adjusted by noncovalent intermolecular forces. Choosing triamcinolone acetonide (TA) as a model drug, the skin penetration studies revealed that DES-RM significantly enhanced TA penetration and retention in comparison with their corresponding DES and oil. Furthermore, in vivo animal experiments demonstrated that TA@DES-RM exhibited good anti-psoriasis therapeutic efficacy as well as biocompatibility.
The present study offers innovative insights into the optimal design of micellar nanodelivery system based on DES combining experiments and computational simulations and provides a promising strategy for developing efficient transdermal delivery systems for sparingly soluble drugs.
由于溶解度低和渗透性差，透皮递药对于脂溶性差的药物具有挑战性。深共晶溶剂（DES）/或离子液体（IL）介导的纳米载体越来越受到关注。然而，它们中的大多数需要添加辅助材料（如表面活性剂或有机溶剂）来维持制剂的稳定性，这可能会引起皮肤刺激和潜在毒性。
我们使用天然氧化苦参碱和月桂酸制备了一种两亲性 DES，并基于该 DES 的特性构建了一种新型自组装反向胶束系统（DES-RM）。合成的 DES 表现出宽的液体窗口，显著增溶了一系列脂溶性差的药物，并且进一步建立了具有良好预测能力的定量构效关系（QSAR）模型。实验和分子动力学模拟阐明了 DES-RM 的自组装是通过非共价分子间力来调节的。选择曲安奈德（TA）作为模型药物，皮肤渗透研究表明，与相应的 DES 和油相比，DES-RM 显著增强了 TA 的渗透和保留。此外，体内动物实验表明，TA@DES-RM 表现出良好的抗银屑病治疗效果和生物相容性。
本研究通过实验和计算模拟为基于 DES 的胶束纳米递药系统的优化设计提供了新的见解，并为开发脂溶性差药物的高效透皮递药系统提供了有前景的策略。
