【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(xì)胞內(nèi)測(cè)定阿霉素濃度的HPLC檢測(cè)方法,研究PAMAM對(duì)阿霉素在HepG 2細(xì)胞內(nèi)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(jìn)入PAMAM內(nèi)腔制備載藥膠束,以柔紅霉素為內(nèi)標(biāo),粉碎細(xì)胞后提取細(xì)胞內(nèi)的阿霉素進(jìn)行濃度測(cè)定。測(cè)定細(xì)胞攝取、外排期間的藥物濃度,繪制時(shí)間-濃度曲線,并計(jì)算動(dòng)力學(xué)參數(shù)。結(jié)果 PAMAM包裹脫鹽酸阿霉素后得到阿霉素的質(zhì)量濃度為1.034g·L-1的溶液,成功建立胞內(nèi)阿霉素的含量測(cè)定方法。細(xì)胞攝取動(dòng)力學(xué)結(jié)果顯示PAMAM使得阿霉素胞內(nèi)達(dá)峰時(shí)間為1h,胞內(nèi)濃度明顯增高;消除動(dòng)力學(xué)結(jié)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(jié)論經(jīng)PAMAM包裹后阿霉素能夠在HepG 2細(xì)胞內(nèi)快速達(dá)峰,胞內(nèi)濃度增加,消除速率減慢,滯留時(shí)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(xué)藥學(xué)院;清華大學(xué)深圳研究生院生命與健康學(xué)部;
【基金】：廣東省自然科學(xué)基金(S2012040006829)
【分類號(hào)】：R96

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