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目的制备雷公藤红素纳米混悬剂,并进行体内外抗肿瘤作用研究。方法采用超声注入联合旋转蒸发法制备雷公藤红素纳米混悬剂,以粒径大小为指标,筛选合适的稳定剂;采用动态光散射法、透射电镜考察粒径和形态,并对其不同介质稳定性、体外释放、溶血性、体外抗肿瘤活性进行研究;建立H22荷瘤小鼠模型,以雷公藤红素注射液为对照组,2 mg/kg iv给药,考察体内抗肿瘤作用。结果聚乙二醇-聚己内酯(m PEG2000-PCL2000)为雷公藤纳米混悬剂的优良的稳定剂,所制备的纳米混悬剂粒径为(67.1±3.0)nm,Zeta电位为(-10.4±1.45)m V,多分散性指数为0.232±0.08,近乎为球形,分布比较均匀。在磷酸缓冲液(PBS)、血浆、生理盐水、5%葡萄糖中均稳定;体外缓慢释放,在144 h累积释放率达到74.04%;MTT结果显示雷公藤红素纳米混悬剂对HepG2细胞的毒性强于溶液(IC50,1.179μg/m L vs 2.377μg/m L,P<0.05)。体内研究中雷公藤红素纳米混悬剂对H22荷瘤小鼠的的抑瘤率显著高于注射液组(70.36%vs 51.1%,P<0.05)。结论制备的雷公藤红素纳米混悬剂粒径小、载药量高、稳定性好,显著提高了雷公藤红素的抗肿瘤效果,可以作为雷公藤红素作为抗肿瘤药物应用的合适剂型。
OBJECTIVE To prepare tripterine nanosuspensions and study the anti-tumor effects in vitro and in vivo. Methods Celastrol nanosuspensions were prepared by ultrasonic injection combined with rotary evaporation. The size of the particles was used as an index to screen the suitable stabilizers. The particle size and morphology were investigated by dynamic light scattering and transmission electron microscopy. Stability, in vitro release, hemolytic, antitumor activity in vitro. The H22 tumor-bearing mouse model was established. The tripterygium injection was used as the control group and administered with 2 mg / kg iv. The antitumor activity in vivo was investigated. Results Polyethylene glycol-polycaprolactone (m PEG2000-PCL2000) was an excellent stabilizer for the tripterygium wilfordii suspension. The prepared nanosuspension was (67.1 ± 3.0) nm and the zeta potential was ( -10.4 ± 1.45) m V, polydispersity index was 0.232 ± 0.08, almost spherical, the distribution is more uniform. It was stable in phosphate buffered saline (PBS), plasma, normal saline and 5% glucose, and slowly released in vitro. The cumulative release rate reached 74.04% at 144 h. MTT results showed that the toxicity of tripterine nanosuspension to HepG2 cells Stronger than the solution (IC50, 1.179 μg / m L vs 2.377 μg / m L, P <0.05). In vivo, tripterine nanosuspension had significantly higher tumor inhibition rate in H22 tumor-bearing mice than in injection group (70.36% vs 51.1%, P <0.05). Conclusion Tripton Nano suspension prepared with small particle size, high drug loading, good stability, significantly enhance the anti-tumor effect of tripterine, which can be used as a suitable dosage form for antineoplastic drugs .