SD大鼠口服姜黄素-白蛋白纳米粒的药代动力学研究

摘要

目的 明确白蛋白纳米粒制剂对大鼠口服姜黄素在体内药代动力学的影响.方法 建立大鼠血浆中姜黄素的HPLC测定方法,色谱柱为COSMOSIL 5C18柱,流动相为5％冰醋酸溶液∶乙腈=26∶74(V/V),流速为1mL·min-1,检测波长为433 nm.采用反溶剂沉淀-超声破碎法制备姜黄素-白蛋白纳米粒,按照100 mg·kg-1的剂量灌胃给予SD大鼠后于不同时间点测定血浆中药物浓度,计算相应的药代动力学参数.结果 所得HPLC方法的专属性较高,血浆中姜黄素在0.02～10μg·mL-1范围内具有良好的线性关系,精密度及稳定性均符合要求.姜黄素原料药和姜黄素-白蛋白纳米粒在大鼠体内的AUC分别为(1.312±0.299)μg·(h·mL)-1、(1.774±0.288)μg·(h·mL)-1;tmax分别为(1.147±0.204)h、(0.417±0.129)h;Cmax分别为(0.091±0.028)μg·mL-1、(0.282±0.065)μg·mL-1.结论 姜黄素-白蛋白纳米粒能显著加快大鼠口服后的药物吸收并提高其生物利用度.%ObjectiveTo investigate the effect of albumin nanoparticles on the pharmacokinetics of curcumin after oral administration in rats.Methods The HPLC method for determination of curcumin in rat plasma was established.The separation was performed on a COSMOSIL 5C18 column with a mobile phase of 5％glacial acetic acid-acetonitrile (26∶74, V/V) and the detection wave length of 433 nm.Curcumin-albumin nanoparticles were prepared under ultra-sonication using anti-solvent precipitation method.The plasma concentration of curcumin was determined at predetermined time after SD rats were intragastrically administrated with a single dose of 100 mg·kg-1, then the corresponding pharmacokinetic parameters were calculated.Results The HPLC method showed a high specificity.A good linearity of curcumin in plasma was obtained over the range of0.02-10μg·m L-1.Precision and stability met the analytical requirements.The AUC of curcumin and nanoparticles after oral administration in rats were (1.312±0.299) and (1.774±0.288) μg· (h·m L) -1, tmaxvalues were (1.147±0.204) and (0.417±0.129) h;Cmaxvalues were (0.091±0.028) and (0.282±0.065) μg·m L-1, respectively.ConclusionThe curcumin-albumin nanoparticles could significantly accelerate the absorption and improve thebioavailability of curcumin after oral administration in rats.