目的 制备柴达木枸杞籽油纳米乳（LN），并评价其对日光性皮炎小鼠的治疗效果。方法 以离心乳层保留率（CR）为评价指标，采用单因素实验结合Box-Benhnken设计-效应面法（BBD-RSM）优化LN的处方及制备工艺；通过透射电子显微镜（TEM）观察纳米乳微观形态；测定其pH值、粒径、多分散系数（PDI）、Zeta电位、黏度、包封率（EE）及载药量（DL），并通过室温储存实验、离心实验初步评价其稳定性；采用人永生化角质形成细胞（Ha Ca T细胞）初步评估其生物安全性；建立紫外线（UV）诱导的BALB/c小鼠急性日光性皮炎模型，评价LN的治疗效果。结果 LN的最佳制备工艺条件为：乳化时间10 min、乳化温度75℃、乳化剂添加量16%、增稠剂添加量0.6%（增稠剂比例8∶2）、柴达木枸杞籽油添加量6%，此条件下制备LN的CR为94.92%。TEM观察显示，LN为乳白色近球形液滴，分散均匀；其理化指标检测结果为：pH值5.78±0.02，粒径（93.33±9.53）nm,PDI为0.22±0.02,Zeta电位（-31.43±0.36）m V，黏度0.37 Pa·s,EE为84.01%,DL为4.29%。稳定性实验表明，LN在室温放置30 d及不同离心条件下，外观性状无明显异常，粒径及PDI无显著变化，稳定性良好；细胞实验显示，LN对HaCaT细胞活力无明显影响，生物安全性良好。动物实验结果显示，与模型组相比，LN各剂量组均能有效缓解UV诱导的小鼠皮肤红斑、结痂及脱屑症状，显著提升小鼠皮肤组织中过氧化氢酶（CAT）和超氧化物歧化酶（SOD）活力，降低基质金属蛋白酶（MMP）-3和MMP-9含量（P<0.01）；其中LN高、中剂量组可显著降低炎症因子白细胞介素（IL）-6、IL-1β水平（P<0.01）。结论 制备的LN在理化性能、稳定性及生物安全性方面表现优异，且对UV诱导的小鼠急性日光性皮炎具有显著治疗效果，是一种极具应用前景的外用纳米乳制剂。

Objective To prepare nanoemulsion of seeds oil of Lycium barbarum from Qaidam Basin(LN) and evaluate its therapeutic effect on mice with solar dermatitis. Methods The centrifugal retention rate(CR) was used as the evaluation index. The single factor experiment combined with Box-Behnken response surface design method(BBD-RSM) was adopted to optimize the prescription and preparation process of LN. The microscopic morphology of LN was observed by transmission electron microscopy(TEM). The pH value, particle size, polydispersity index(PDI), Zeta potential, viscosity, encapsulation efficiency(EE) and drug loading(DL) of LN were determined. The stability of LN was preliminarily evaluated by room temperature storage experiment and centrifugation experiment. The biological safety of LN was preliminarily evaluated by human immortalized keratinocyte(HaCaT cells). The acute solar dermatitis model of BALB/c mice was established by ultraviolet(UV) irradiation to evaluate the therapeutic effect of LN. Results The optimal preparation process of LN was as follows: emulsification time 10 min, emulsification temperature 75 ℃, emulsifier addition 16%, thickener addition 0.6%(thickener ratio 8∶2), and seeds oil of L. barbarum from Qaidam Basin addition 6%. Under these conditions, the CR of LN was 94.92%. TEM observation showed that LN was a milky white nearly spherical droplet with uniform dispersion. The physical and chemical index detection results were as follows: pH value 5.78 ± 0.02, particle size(93.33 ± 9.53) nm, PDI 0.22 ± 0.02, Zeta potential(-31.43 ± 0.36) mV, viscosity 0.37 Pa·s, EE 84.01%, and DL 4.29%. The stability experiment showed that LN had no obvious abnormal appearance after being placed at room temperature for 30 days and under different centrifugation conditions. There was no significant change in particle size and PDI, and the stability was good. The cell experiment showed that LN had no significant effect on the viability of HaCaT cells, and the biological safety was good. The animal experiment results showed that compared with the model group, all dose groups of LN could effectively alleviate the symptoms of skin erythema, scabbing and desquamation induced by UV in mice, significantly increase the activities of catalase(CAT) and superoxide dismutase(SOD) in mouse skin tissue, and reduce the contents of matrix metalloproteinase(MMP)-3 and MMP-9(P < 0.01). Among them, the high and medium dose groups of LN could significantly reduce the levels of inflammatory factors interleukin(IL)-6 and IL-1β(P < 0.01). Conclusion The prepared LN has excellent physical and chemical properties, stability and biological safety, and has a significant therapeutic effect on acute solar dermatitis induced by UV in mice. It is a nanoemulsion formulation with great application prospects for external use.

R283.6;R285.5

青海省中央引导地方科技发展资金计划项目(2025ZY011)