目的 制备一种新型离子液体纳米乳凝胶贴膏（ionic liquid-based nanoemulsion gel paste，IL-NGP），用于抗疖中药复方（anti-furuncle herbal combinations，FHC）提取物经皮给药治疗疖痈。方法 以棕榈酸异丙酯为油相，筛选出聚山梨酯-80为乳化剂，丙二醇为助乳化剂，采用油、乳化剂和助乳化剂的用量为考察因素，纳米乳（nanoemulsions，NEs）的粒径和多分散指数（polydispersity index，PDI）为考察指标，使用Box-Behnken设计-响应面法（Box-Behnken design-response surface method，BBD-RSM）优化NEs的处方，并对最佳处方进行验证。将胆碱碳酸氢盐-己烯酸离子液体（ionic liquid，IL）引入NEs，形成IL-NEs。以感官评价、初黏力、持黏力为评价指标，通过单因素试验考察各辅料及IL-NEs用量，优化出最佳IL-NGP处方。通过稳定性试验、皮肤渗透试验和抗菌活性测定对IL-NGP进行体外评价，并采用药效学模型、疼痛模型和小鼠耳肿胀模型考察IL-NGP的体内疖痈治疗效果。结果 成功制备了IL-NGP，其稳定性良好，与传统凝胶膏（gel paste，GP）相比，IL-NGP的抑菌效果提高1.32倍，其在48 h内的蟾毒灵释放量提高2.42倍，并对二甲苯致小鼠耳肿胀、扭体疼痛、小鼠肉芽棉球增生、角叉菜胶引起的大鼠足趾肿胀有较好的抑制作用。结论 将传统中药方FHC制备成一种新型经皮递送的离子液体基质的NGP，其透皮性能优良，疖痈治疗效果显著。

Objective To develop a novel ionic liquid-based nanoemulsion gel paste (IL-NGP) for the transdermal delivery of anti-furuncle herbal combination (FHC) extracts in the treatment of furunculosis. Methods Isopropyl palmitate was used as the oil phase, and Tween-80 as the surfactant with propylene glycol as the co-surfactant. The mass ratios of oil, surfactant, and co-surfactant were considered as factors, while the particle size and polydispersity index (PDI) of the nanoemulsions (NEs) were the evaluation indicators. The Box-Behnken design-response surface methodology (BBD-RSM) was applied to optimize the formulation of NEs, and the optimal formulation was validated. Choline bicarbonate-hexenoic acid ionic liquid (IL) was introduced into NEs to form IL-NEs. Sensory evaluation, initial adhesion, and retention adhesion were used as assessment indices, and the effects of different excipients and IL-NEs content were studied through single-factor experiments to optimize the best IL-NGP formulation. The IL-NGP was evaluated in vitro through stability tests, skin permeability tests, and antimicrobial activity assays. In vivo efficacy was assessed through pharmacological models, pain models, and mouse ear edema models to evaluate the therapeutic effects on furunculosis. Results The IL-NGP was successfully prepared with good stability. Compared to traditional gel paste (GP), IL-NGP exhibited a 1.32 times higher antibacterial effect and a 2.42 times higher bufalin release within 48 h, and showed better inhibition on xylene-induced mouse ear edema, writhing pain, granuloma formation in mice, and carrageenan-induced rat paw edema. Conclusion The traditional Chinese medicine formula FHC was developed into a novel transdermal ionic liquid-based NGP, exhibiting excellent skin permeability and significant therapeutic effects in furunculosis treatment.

R283.6

国家自然科学基金项目（21775061）；山东省泰山青年学者计划（tsqn202211136）；山东省高等学校青创人才引育计划（2021505031）；济南市高校20项创新计划项目（202228085）；山东省自然科学基金项目（ZR2022QH159）