丹皮酚纳米乳的制备及血管内皮细胞摄取的考察
Preparation of paeonol nanoemulsion and investigation of vascular endothelial cells uptake
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摘要: 为了改善丹皮酚（paeonol，Pae）水溶性差以及生物利用度低等缺陷，进行丹皮酚纳米乳（paeonol-nanoemulsion，Pae-NE）制备研究，并考察了人脐静脉内皮细胞株（human umbilical vein endothelial cells，HUVECs）对Pae-NE的摄取效果。采用相转变法制备Pae-NE，单因素初步筛选和星点设计-效应面法（CCD）优化Pae-NE的处方，并进行药剂学性能表征。MTT法考察Pae-NE的HUVECs毒性；荧光显微镜、流式细胞仪研究HUVECs对Pae-NE的摄取效率。结果显示：Pae-NE最优处方为Pae 20 mg、LCT 55.1 mg、MCT 144.9 mg、HS15 600 mg和1，2丙二醇200 mg。所得Pae-NE外观呈淡蓝色乳光，平均粒径为（25.69 ± 0.03）nm，PDI为0.182 ± 0.09，Zeta电位为-（4.01 ± 0.30）mV；载药量为（1.967 ± 0.28） mg/mL、包封率为（99.36 ± 0.1）%；Pae质量浓度在10-1 ~ 10-3 μg/mL范围内对HUVECs生长无显著影响，且NE作为药物递送载体能显著增强Pae在HUVECs上的摄取效率。本研究结果表明，Pae-NE制备方法简单，稳定性好，并且可以促进HUVECs对Pae的摄取效率，提示NE是脂溶性药物Pae较好的剂型选择。Abstract: In order to improve the poor solubility and low bioavailability of paeonol (Pae), paeonol-nanoemulsion (Pae-NE) was prepared, and its effect on uptake of human umbilical vein endothelial cells (HUVECs) was investigated.Pae-NE was prepared by phase inversion composition (PIC), the formulation of Pae-NE was optimized by single factor method and central composite design-response surface method (CCD), and the pharmaceutical properties were further characterized.Moreover, MTT was applied to evaluate the toxicity of Pae-NE on HUVECs, and the cellular uptake efficiency of Pae-NE was detected by fluorescence microscopy and flow cytometry.The results showed that the optimal formulation of Pae-NE was 20 mg of Pae, 55.1 mg of LCT, 144.9 mg of MCT, 600 mg of HS15, and 200 mg of 1,2 propylene glycol.The Pae-NE appearance was a light blue emulsion, and the average particle size is (25.69 ± 0.03) nm, with PDI of 0.182 ± 0.09, Zeta potential of -(4.01 ± 0.30) mV and good stability.The drug loading of Pae-NE was (1.967 ± 0.28) mg/mL and encapsulation rate of (99.36 ± 0.1)%.Pae-NE performed no significant effect on HUVECs growth in the Pae concentration range of 10-1-10-3 μg/mL.Moreover, NE as a drug delivery carrier significantly enhanced the uptake efficiency of Pae on HUVECs.In conclusion, Pae-NE preparation method was simple and stable, and promotes HUVECs uptake efficiency of Pae, suggesting that NE was a better dosage form reference for the lipid-soluble drug of Pae.
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Keywords:
- paeonol /
- nanoemulsion /
- preparation /
- human umbilical vein endothelial cells /
- cell uptake
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