【摘要】：目的利用聚酰胺-胺(polyamidoamine,PAMAM)樹枝狀大分子包裹抗癌藥物阿霉素,建立細胞內測定阿霉素濃度的HPLC檢測方法,研究PAMAM對阿霉素在HepG 2細胞內的攝取行為的影響。方法將鹽酸阿霉素脫去鹽酸后利用疏水作用進入PAMAM內腔制備載藥膠束,以柔紅霉素為內標,粉碎細胞后提取細胞內的阿霉素進行濃度測定。測定細胞攝取、外排期間的藥物濃度,繪制時間-濃度曲線,并計算動力學參數(shù)。結果 PAMAM包裹脫鹽酸阿霉素后得到阿霉素的質量濃度為1.034g·L-1的溶液,成功建立胞內阿霉素的含量測定方法。細胞攝取動力學結果顯示PAMAM使得阿霉素胞內達峰時間為1h,胞內濃度明顯增高;消除動力學結果顯示,k減小為原來的0.347倍,t1/2延長為原來的2.878倍,MRT增加為原來的2倍。結論經PAMAM包裹后阿霉素能夠在HepG 2細胞內快速達峰,胞內濃度增加,消除速率減慢,滯留時間延長,有利于藥物藥效的發(fā)揮。
[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.
【作者單位】： 沈陽藥科大學藥學院;清華大學深圳研究生院生命與健康學部;
【基金】：廣東省自然科學基金(S2012040006829)
【分類號】：R96

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