目的 基于“药辅合一”理念，构建牛至精油-石榴皮多酚纳米乳（Origanum vulgare essential oil and Granati Pericarpium polyphenols nanoemulsion，OVEO-GPP-NE）阴道递药系统，并对其进行处方筛选、理化性质表征及体外透黏膜性能、抑菌活性评价。方法 应用伪三元相图与形态观察法筛选纳米乳的处方，并对纳米乳乳剂类型、微观形态、粒径、ζ电位、多分散指数（polydispersity index，PDI）、pH值、稳定性等理化性质进行表征。通过体外透黏膜实验和抑菌活性实验研究OVEO-GPP-NE在阴道黏膜处的药物递送效果。结果 OVEO-GPP-NE最优处方：OVEO、GPP、肉豆蔻酸异丙酯（IPM）、聚氧乙烯氢化蓖麻油（RH-40）、聚山梨酯-80（Tween-80，T80）、Transcutol^® P二乙二醇单乙醚（diethylene glycol monoethyl ether，DGME）、水质量比为2.00∶3.00∶7.00∶8.55∶5.70∶4.75∶69.00；按最优处方所制OVEO-GPP-NE外观澄清透明，乳剂类型为O/W型，平均粒径为（25.49±0.21）nm，PDI为0.43±0.05，ζ电位为（−16.73±0.35）mV，透射电子显微镜观察结果显示，OVEO-GPP-NE的乳滴呈球形，外观圆整，大小在25 nm内。OVEO-GPP-NE离心稳定性、放置稳定性良好，pH值为3.92±0.02。体外透黏膜性能研究结果表明，OVEO-GPP-NE中石榴皮多酚的累积渗透量是石榴皮多酚纳米乳（Granati Pericarpium polyphenols nanoemulsion，GPP-NE）的2.8倍、黏膜滞留量是GPP-NE的1.61倍。抑菌活性实验结果表明，OVEO-GPP-NE对金黄色葡萄球菌Staphylococcus aureus、耐甲氧西林金黄色葡萄球菌methicillin-resistant S. aureus（MRSA）、大肠杆菌Escherichia coli均具有较好的抑菌效果，其中石榴皮多酚与牛至精油对2种金黄色葡萄球菌表现出协同抑菌效果。结论 基于“药辅合一”理念，成功构建了OVEO-GPP-NE递药系统，为需氧菌性阴道炎的治疗提供了可行方案。

Objective To construct a vaginal drug delivery system of Origanum vulgare essential oil and Granati Pericarpium polyphenols nanoemulsion (OVEO-GPP-NE), screen the prescription, characterize the physicochemical properties, evaluate the in vitro transmucosal properties and antibacterial activity based on the concept of “unification of medicines and excipients”. Methods Pseudo-ternary phase diagram and morphological observation were applied to determine the prescription of the nanoemulsion. The type, microscopic morphology, average droplet size, ζ potential, polydispersion index (PDI), pH and stability of OVEO-GPP-NE were characterized. The drug delivery effect of OVEO-GPP-NE at the vaginal mucosa was investigated by in vitro transmucosal assay and bacteriostatic activity assay. Results The optimal prescription mass ratio of OVEO-GPP-NE was OVEO: GPP: isopropyl myristate (IPM): polyoxyethylene hydrogenated castor oil (RH-40): Tween-80, (T80): Transcutol^® P diethylene glycol monoethyl ether (DGME): water as (2.00:3.00:7.00:8.55:5.70:4.75:69.00). The type of emulsion was O/W and the appearance of OVEO-GPP-NE made according to the optimal prescription was clear and transparent. The average particle size was (25.49 ±0.21) nm, the PDI was 0.43 ±0.05, the ζ potential was (−16.73 ±0.35) mV. The results of transmission electron microscopy showed that the emulsion droplets of OVEO-GPP-NE were spherical in shape, round in appearance, and within 25 nm in size. The centrifugal stability and placement stability of OVEO-GPP-NE were good, and the pH was 3.92 ±0.02. The in vitro permeation results showed that the cumulative drug penetration of GPP in OVEO-GPP-NE was 2.85 times higher and the mucosal retention was 1.61 times higher than that of Granati Pericarpium polyphenols nanoemulsion (GPP-NE). The results of bacteriostatic activity showed that OVEO-GPP-NE was effective against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Escherichia coli, in which GPP and OVEO showed synergistic bacteriostatic effects on two kinds of S. aureus. Conclusion Based on the concept of “unification of medicines and excipients”, this study successfully constructed the OVEO-GPP-NE drug delivery system, which provides a feasible solution for the treatment of aerobic vaginitis.

R283.6

新疆维吾尔自治区“天山英才科技创新领军人才”培养计划（2023TSYCLJ0044）；新疆维吾尔自治区自然科学基金杰出青年科学基金（2024D01E33）