雷公藤红素纳米混悬剂的制备及其抗肿瘤作用研究

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,P0.05)。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%,P0.05)。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。

Preparation and anti-tumor activity of Celastrol Nanoparticles

Objective To prepare Celastrol Nanoparticles and study its anti-tumor activities in vitro andin vivo.Methods Celastrol nanosuspensions were prepared by microprecipitation combined with evaporation method. Suitable stabilizer was screened according to the size of the resultant nanosuspensions. Dynamic light scattering method was used to measure the particle size and transmission electron microscopy was used to observe the morphology. The stability in different medium, drug release in vitro, the hemolysis and the cytotoxicity were studied. Anti-tumor effectin vivo was investigated on H22-bearing mice using Celastrol Injections as the control at the dose of 2 mg/kg.Results Polyethylene glycol-polycaprolactone (mPEG2000-PCL2000) was a good stabilizer for Celastrol Nanoparticles. Celastrol Nanoparticles had (67.1 ± 3.0) nm in diameter with a polydisperse index of (0.23 ± 0.08) and a Zeta potential of (?10.4 ± 1.5) mV. Celastrol Nanoparticles were nearly spherical in morphology and had a more uniform distribution. They were quite stable in PBS, normal saline, 5% glucose, and plasma. Celastrol Nanoparticles showed sustained drug release and the cumulative release reached 74.04% within 144 h. MTT assay displayed that Celastrol Nanoparticles had stronger cytotoxicity against HepG2 cells than free c elastrol (IC50, 1.179μg/mLvs2.377μg/mL,P< 0.05). It was demonstrated that Celastrol Nanoparticles significantly improved the therapeutic efficacyin vivoon H22-bearing mice in contrast to Celastrol Injections
(70.36%vs 51.1%,P< 0.05).Conclusion Celastrol nanosuspensions have characteristics of small particle size, high drug-loading content, and good stability, which significantly improve the anti-tumor effect of celastrol, and it is believed to be suitable dosage form for the application of celastrol in tumor treatment.