[关键词]
[摘要]
目的 构建当归精油纳米乳(Angelica Sinensis Radix essential oil-loaded nanoemulsion,AEO-NE)递药系统并对其进行表征及稳定性、毛囊靶向、毛发生长促进作用评价。方法 分别应用伪三元相图法和星点设计-响应面法(central composite experiment design-response surface method,CCD-RSM)对纳米乳处方进行筛选和优化。对纳米乳乳剂类型、粒径、ζ电位、多分散指数(polydispersity index,PDI)、微观形态、黏度、pH值进行表征。以粒径、PDI、外观变化及Z-藁本内酯含量为指标,评价最优处方纳米乳离心稳定性、放置稳定性以及稀释稳定性。通过在体给药荧光标记的AEO-NE于小鼠背部皮肤研究制剂毛囊靶向能力。应用C57BL/6小鼠研究AEO-NE体内促进毛发生长的作用。结果 AEO-NE最优处方为AEO-辛基酚聚氧乙烯醚10(OP-10)-无水乙醇-水(2.25∶0.75∶1∶96);按最优处方所制AEO-NE外观澄清、透明、微泛蓝光,乳剂类型为O/W型,平均粒径为(15.95±0.33)nm,PDI为0.11±0.02,ζ电位为(-0.14±0.10)mV,pH值为5.89±0.16,黏度为(1.57±0.08)mPa·s,透射电镜结果表明AEO-NE乳滴呈球形,外观圆整,大小在20 nm内。AEO-NE离心稳定性、稀释稳定性良好,在4 ℃条件下密封避光放置稳定性良好,粒径及Z-藁本内酯含量无显著变化。AEO-NE局部皮肤给药24 h内均表现出毛囊靶向性,具有促进毛发生长的作用。结论 基于“药辅合一”理念,成功构建了以AEO为唯一油相的AEO-NE,其宏观及微观形态、相关理化性质符合纳米乳制剂要求,稳定性良好,在靶向促进毛发生长方面具有一定潜力。
[Key word]
[Abstract]
Objective To prepare, characterize Angelica Sinensis Radix essential oil (AEO)-loaded nanoemulsion (AEO-NE) and evaluate on its hair follicle targeted capacity, hair growth promoting effect and stability. Methods The pseudo-ternary phase diagram method and central composite design-response surface method (CCD-RSM) were used to screen and optimize the prescription of AEO-NE, respectively. The type, average droplet size, ζ potential, polydispersion index (PDI), microscopic morphology, viscosity and pH of AEO-NE were characterized. The centrifugation stability, placement stability and dilution stability of the optimized AEO-NE were evaluated with particle size, PDI, appearance change and content of Z-ligustilide as indicators. The hair follicle targeted ability of AEO-NE was investigated by administrating fluorescin-labeled AEO-NE to the back skin of mice in vivo. The promoting effect of AEO-NE on hair growth was studied in C57BL/6 mice. Results The optimized formula of AEO-NE consisted 2.25% octylphenol polyoxyethylene ether 10 (OP-10), 0.75% absolute ethanol, 1% AEO and 96% water; The appearance of the optimized AEO-NE was clear, transparent and slightly blue. The emulsion type is O/W type, the average particle size was (15.95 ± 0.33) nm, the PDI was 0.11 ± 0.02, the ζ potential was (-0.14 ± 0.10) mV, the pH value was 5.89 ± 0.16, and the viscosity was (1.57 ± 0.08) mPa·s. The result of transmission electron microscope showed that AEO-NE was spherical and round, and its size was within 20 nm. AEO-NE had good stability in centrifugation and dilution, and was stable at 4 ℃ avoiding light with no significant changes in droplet size and Z-ligustilide content. AEO-NE showed hair follicle targeted property within 24 h with local skin administration, and had the effect of promoting hair growth. Conclusion Based on the concept of “combination of drugs and adjuvants”, the AEO-NE with AEO as the only oil phase was successfully constructed. Its macro- and micro-morphology, related physical and chemical properties met the requirements of nanoemulsion preparation. With good stability, AEO-NE had certain potential in hair follicle-targeted promoting hair growth.
[中图分类号]
R283.6
[基金项目]
四川省科技厅项目(2019ZYZF0171)