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评价鬼臼毒素(PPT)被固体脂质纳米粒(SLN)包裹前、后的抗肿瘤效果以及在动物体内的药代动力学特点.建立昆明小鼠S180肉瘤模型,将PPT-SLN、PPT分别以5mg/kg的等效剂量对小鼠每天腹腔注射,连续3周,每天量取肿瘤体积,并观察小鼠状态、体重的变化.末次给药24h后处死小鼠,剥取瘤块称重,计算抑瘤率.将PPT-SLN、PPT以10mg/kg的等效剂量对小鼠腹腔注射,于不同时间点采血,以HPLC分析血液中PPT的含量,绘制血药浓度-时间曲线,并计算药代动力学参数.研究发现,肿瘤小鼠在连续腹腔注射PPT-SLN后,肿瘤体积与重量比对照组、PPT组明显降低,抑瘤率达58.13%,抑瘤效果显著,且小鼠体重增加量比PPT组多.药代动力学结果显示,在被纳米载体包裹后,PPT在血药中的浓度得到了提升,释放时间有所延长,生物利用度也有较大提高.结果表明SLN包裹PPT能够有效地提高其血药浓度,起到缓释效果,提高其抗肿瘤活性,并降低毒性,具有较好的应用前景.
To evaluate the anti-tumor effects of podophyllotoxin (PPT) encapsulated in solid lipid nanoparticles (SLN) and its pharmacokinetics in vivo.METHODS Kunming mouse S180 sarcoma model was established, and the PPT-SLN and PPT The mice were injected intraperitoneally with 5 mg / kg ip for 3 consecutive weeks, and the tumor volume was measured every day, and the changes of the mice state and body weight were observed.The mice were sacrificed 24h after the last administration, , The tumor inhibition rate was calculated.The PPT-SLN and PPT were intraperitoneally injected into the mice at the equivalent dose of 10 mg / kg, blood samples were taken at different time points, the content of PPT in the blood was analyzed by HPLC, and the plasma concentration-time curve Calculate the pharmacokinetic parameters.The study found that after continuous intraperitoneal injection of PPT-SLN in tumor mice, tumor volume and weight ratio of the control group and the PPT group was significantly reduced, the inhibition rate was 58.13%, the anti-tumor effect was significant, and the mice The results of pharmacokinetics showed that the concentration of PPT in blood plasma was increased, the release time prolonged and the bioavailability also increased greatly after being encapsulated by nanocarrier.The results showed that SLN PPT wrapping can effectively increase its blood concentration, play a sustained release effect, improve it Tumor activity and reduced toxicity, has good application prospect.