PAMAM树状大分子对阿霉素在HepG 2细胞中的摄取动力学的影响

发布时间：2018-10-26 12:25

【摘要】：目的利用聚酰胺-胺(polyamidoamine,PAMAM)树枝状大分子包裹抗癌药物阿霉素,建立细胞内测定阿霉素浓度的HPLC检测方法,研究PAMAM对阿霉素在HepG 2细胞内的摄取行为的影响。方法将盐酸阿霉素脱去盐酸后利用疏水作用进入PAMAM内腔制备载药胶束,以柔红霉素为内标,粉碎细胞后提取细胞内的阿霉素进行浓度测定。测定细胞摄取、外排期间的药物浓度,绘制时间-浓度曲线,并计算动力学参数。结果 PAMAM包裹脱盐酸阿霉素后得到阿霉素的质量浓度为1.034g·L-1的溶液,成功建立胞内阿霉素的含量测定方法。细胞摄取动力学结果显示PAMAM使得阿霉素胞内达峰时间为1h,胞内浓度明显增高;消除动力学结果显示,k减小为原来的0.347倍,t1/2延长为原来的2.878倍,MRT增加为原来的2倍。结论经PAMAM包裹后阿霉素能够在HepG 2细胞内快速达峰,胞内浓度增加,消除速率减慢,滞留时间延长,有利于药物药效的发挥。
[Abstract]:Objective to study the effect of polyamidoamine,PAMAM on the uptake of adriamycin in HepG 2 cells by using a HPLC assay to determine the concentration of adriamycin in cells by encapsulating adriamycin with dendritic macromolecules of polyamide-amine (polyamidoamine,PAMAM). Methods doxorubicin hydrochloride was removed from hydrochloric acid and hydrophobic action was used to prepare drug-loaded micelles. Doxorubicin was extracted from the cells and then the concentration of doxorubicin was determined by using daunorubicin as the internal standard. The drug concentration during cell uptake and efflux was measured, time-concentration curve was drawn and kinetic parameters were calculated. Results the solution of doxorubicin hydrochloride was obtained by PAMAM and the concentration of adriamycin was 1.034 g L-1. A method for the determination of adriamycin in cells was established successfully. The results of cell uptake kinetics showed that PAMAM increased the intracellular peak time of adriamycin for 1 hour and the intracellular concentration increased significantly. The results of elimination kinetics show that k decreases by 0.347 times, t 1 / 2 prolongs by 2.878 times and MRT increases by 2 times. Conclusion PAMAM encapsulated adriamycin can rapidly reach the peak, increase the intracellular concentration, slow down the elimination rate and prolong the retention time in HepG 2 cells, which is beneficial to the development of drug efficacy.
【作者单位】：沈阳药科大学药学院;清华大学深圳研究生院生命与健康学部;
【基金】：广东省自然科学基金(S2012040006829)
【分类号】：R96

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