Pharmacokinetics of paclitaxel loaded nanoparticles made with hydrophobically modified Rhizoma Bletillae polysaccharide in rats
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摘要: 目的 建立一种简便、灵敏的测定大鼠尾静脉和灌胃给予胆甾醇琥珀酰基白及多糖载紫杉醇纳米粒子后的血浆药物浓度的HPLC方法，并评价其药动学特征。 方法 以酮康唑为内标，采用AgilentTC-C18色谱柱（250 mm×4.6 mm，5 μm），以甲醇-乙腈-水（45：20：35）为流动相，流速为1.0 ml/min，采用统计矩法计算药动学参数，评价药动学特征。 结果 紫杉醇在大鼠血中浓度在0.5~20 μg/ml范围内线性关系良好（r=0.999 7），准确度和精密度均符合生物样品分析要求。尾静脉注射3种不同取代度的自制纳米粒和紫杉醇注射液后的t1/2分别为3.86、3.76、3.35和2.62 h；灌胃给予自制紫杉醇纳米粒溶液和紫杉醇混悬液后的t1/2分别为5.28和3.72 h。 结论 该测定方法可用于紫杉醇纳米粒子在大鼠体内的药动学研究，且载紫杉醇自组装纳米粒子在体内的滞留时间比紫杉醇注射液和紫杉醇混悬液有明显延长。Abstract: Objective To establish a simple and sensitive method for the determination of plasma drug concentration in rats after intragastrical and intravenous administration of paclitaxel loaded nanoparticles and to evaluate its pharmacokinetic characteristics. Methods AgilentTC-C18 column (250 mm×4.6 mm, 5 μm) was used for HPLC at the flow rate 1 ml/min with ketoconazole as internal standard and methanol acetonitrile water (45:20:35) as the mobile phase. The statistical moment method was applied to calculate the pharmacokinetic parameters and to evaluate pharmacokinetic characteristics. Results There was a good liner relationship (r=0.999 7) when rat blood concentration of Paclitaxel ranged from 0.5 to 20 μg/ml. The accuracy and precision were in line with the requirements of biological sample analysis. The t1/2 were 3.86, 3.76, 3.35 and 2.62 h after intravenous injection of three lab-made paclitaxel nanoparticles and paclitaxel solution via rat tail vein. The t1/2 were 5.28 and 3.72 h respectively after intragastrical administration of lab-made paclitaxel nanoparticles and paclitaxel suspension. Conclusion This method can be used for the pharmacokinetic study of paclitaxel nanoparticles in rats. The paclitaxel loaded nanoparticles exhibited significantly longer in vivo retention time than paclitaxel injection and paclitaxel suspension.
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Key words:
- Rhizoma Bletillae polysaccharide /
- paclitaxel /
- nanoparticles /
- pharmacokinetics
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