丹参酮Ⅱ_A聚乳酸载药纳米粒体内药物分布初步研究

Study on the Pharmacokinetics of Tashinone Ⅱ_A-loaded Polylactic Acid Nanoparticles in Rabbit

目的:建立测定兔体内丹参酮ⅡA的HPLC方法,并考察丹参酮ⅡA聚乳酸载药纳米粒(TS-PLA-NP)兔体内药代动力学特征。方法:家兔耳缘静脉注射TS-PLA-NP和丹参酮ⅡA溶液,在设定时间点从颈静脉取血制样,以吉非罗齐为内标,采用HPLC-MS法测定丹参酮ⅡA在兔体内的血药浓度及药物组织分布,药动学参数采用DAS2.0进行统计。结果:吉非罗齐和丹参酮ⅡA在该条件下的保留时间分别为10.5、14.5 min。TS-PLA-NP在家兔体内的t1/2由丹参酮ⅡA的2.573 h延长到4.117 h;MRT0～∞由2.585 h延长到6.033 h,峰浓度由0.21 mg/L减少到0.134 mg/L。静脉给药后2 h,丹参酮ⅡA纳米药物组肝脏和肿瘤中的浓度均高于丹参酮ⅡA组;丹参酮ⅡA以纳米的剂型给药后2 h,肝脏中的药物浓度提高了5倍以上,肿瘤中的药物浓度提高了近9倍;心、肾、脾、肺等组织中药物浓度均明显降低;血液中浓度下降了近10倍。结论:丹参酮ⅡA聚乳酸载药纳米粒在兔体内具有良好的缓释和肝靶向特征。

Objective：To establish a HPLC method for measuring tashinone Ⅱ_A concentration in rabbit plasma and study the pharmacokinetics of tashinone Ⅱ_A-loaded polylactic acid nanoparticles and tashinone Ⅱ_A injection in rabbits.Methods：A single dose of TS-PLA-NP and TSⅡ_A injection was administered to 8 healthy rabbits via the ear-edge vein,at the set time withdrew the blood and prepared.The concentrations of tashinone Ⅱ_A in plasma were measured by HPLC with gemfibrozil as the internal standard.The pharmacokinetic parameters of TS-PLA-NP and tashinone Ⅱ_A injection were calculated by program DAS2.0.Results：The average retention times of gemfibrozil and tashinone Ⅱ_A were 10.5 and 14.5 min,respectively.The half-life was prolonged from 2.573 h of free tashinone Ⅱ_A to 4.117 h and MRT_0~∞ from 2.585 h to 6.033 h.The max concentration of tashinone Ⅱ_A was reduced from 0.21 to 0.134 mg/L.Conclusion：The method for the pharmacokinetic research of tshinone Ⅱ_A in rabbit plasma is accuracy,rapid and sensitive.TS-PLA-NP shows significant characteristic of delayed-release.