Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200443, China; Key Laboratory of Smart Drug Delivery of MOE, School of Pharmacy, Fudan University, Shanghai 201203, China.
Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200443, China.
Int J Pharm. 2020 Nov 15;589:119842. doi: 10.1016/j.ijpharm.2020.119842. Epub 2020 Sep 3.
This study aimed to exert the synergistic action of ketoconazole (KCZ) and ionic liquids (ILs) for improving antifungal effect. Various ILs were engineered and demonstrated different solubilization capacity for KCZ. Among them, the IL formed by choline and geranic acid ([Ch][Ger]) was the optimal one and able to imporve the solubility of KCZ by around 100-fold. The in vitro antifungal test revealed the [Ch][Ger] significantly inhibited the activity of T. Interdigitale and exerted the synergistic action with KCZ. Compared to Daktarin®, the [Ch][Ger] not only promoted KCZ to penetrate into deep skin layer but also improved in vivo anti-T. Interdigitale activity significantly. Besides, the [Ch][Ger] was able to strip the skin of the lesion site in a flaky manner to remove fungi more thoroughly. However, the skin can recover to be normal state after treatment and there was no evident skin irritation found in [Ch][Ger] group. The ILs may offer promising opportunities to deliver anti-fungal drugs to treat inner skin fungal infections by synergistic action.
本研究旨在发挥酮康唑（KCZ）和离子液体（ILs）的协同作用，以提高抗真菌效果。设计了各种 ILs，并证明它们对 KCZ 具有不同的溶解能力。其中，胆碱和橙花酸形成的 IL([Ch][Ger])是最佳的一种，能够将 KCZ 的溶解度提高约 100 倍。体外抗真菌试验表明，[Ch][Ger]显著抑制 T. Interdigitale 的活性，并与 KCZ 发挥协同作用。与达克宁®相比，[Ch][Ger]不仅促进 KCZ 渗透到深层皮肤层，而且显著提高体内抗 T. Interdigitale 的活性。此外，[Ch][Ger]能够以片状方式剥落病变部位的皮肤，更彻底地去除真菌。然而，治疗后皮肤可以恢复正常状态，并且在[Ch][Ger]组中未发现明显的皮肤刺激。ILs 可能为通过协同作用将抗真菌药物递送至治疗内部皮肤真菌感染提供有希望的机会。
