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羟基喜树碱纳米粒在大鼠体内的药动学、组织分布及靶向性研究
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| 篇名： | 羟基喜树碱纳米粒在大鼠体内的药动学、组织分布及靶向性研究 |
| TITLE： | Pharmacokinetics，Tissue Distribution and Target Evaluation of Hydroxycamptothecin Nanoparticles in Rats |
| 摘要： | 目的：研究羟基喜树碱纳米粒在大鼠体内的药动学及组织分布特征，并探讨其靶向性。方法：将雄性SD大鼠随机分为两组，每组6只，分别单剂量尾静脉注射羟基喜树碱纳米粒和市售羟喜树碱注射液（4mg/kg，以羟基喜树碱计），在给药后5、30、60、120、240、360、480、600、720min时于眼底静脉丛取血500μL，采用高效液相色谱法测定不同时间点血浆中羟基喜树碱的含量，以DAS3.0等软件计算药动学参数。另取雄性SD大鼠随机分为两组，每组24只，分别单剂量尾静脉注射羟基喜树碱纳米粒和市售羟喜树碱注射液（0.6mg/kg，以羟基喜树碱计），在给药后30、60、120、240min时于腹主动脉取血并摘取心、肝、脾、肺、肾、脑，采用高效液相色谱法测定不同时间点血浆及组织中羟基喜树碱的含量，考察其分布特征及靶向性。结果：羟基喜树碱纳米粒和市售羟喜树碱注射液在大鼠体内均符合二室模型，羟基喜树碱纳米粒的AUC0-720min和AUC0-∞分别为市售羟喜树碱注射液的1.89和1.87倍，MRT0-720min和MRT0-∞为2.74和3.00倍，t1/2β为2.75倍，组间比较差异均有统计学意义（P＜0.05）；给药后30min时，羟基喜树碱纳米粒和注射液在肺中浓度最高；随着时间的推移，药物逐渐向肝部位积累，在60min时肝药浓度达到最高。羟基喜树碱纳米粒在肝的相对摄取率最大（6.28）；以肝为靶向器官，其在心、脾、肺、肾、脑和血浆中的靶向效率均大于羟喜树碱注射液；给药后30～120min，羟基喜树碱纳米粒在心、肺（除给药后30min外）、肾、脑、血浆中的选择性指数均显著高于羟喜树碱注射液（P＜0.05或P＜0.01）。结论：羟基喜树碱纳米粒延长了药物的半衰期、提高了其血药浓度、延长了其体内作用时间，且肝靶向性显著。 |
| ABSTRACT： | OBJECTIVE：To study the pharmacokinetics and tissue distribution characteristics of Hydroxycamptothecin （HCPT） nanoparticles in rats ，and to investigate their targeting. METHODS ：Male SD rats were randomly divided into 2 groups，with 6 rats in each group. They were given HCPT nanoparticles and HCPT injection （4 mg/kg based on HCPT ）via tail vein respectively. 500 μL fundus venous plexus blood were sampled at 5，30，60，120，240，360，480，600 and 720 min after administration. The plasma concentration of HCPT in rats were measured by HPLC at different time points. The pharmacokinetic parameters were calculated by DAS 3.0 software. Male SD rats were randomly divided into two groups ，with 24 rats in each group. They were given HCPT nanoparticles and HCPT injection （0.6 mg/kg based on HCPT ）via tail vein ，respectively. Blood was immediately taken from the abdominal aorta ，and heart ，liver，spleen，lung，kidney and brain were removed at 30，60，120，240 min after administration. The plasma and tissue concentration of HCPT in rats were measured by HPLC. The distribution of HCPT ineach tissue and targeting were investigated. RESULTS ：HCPT nanoparticles and its injection conformed to a two-compartment model in rats. Compared with HCPT injection ，AUC0-720 min andAUC0- ∞ increased by 1.89 and 1.87 times respectively ， MRT0-720 min and MRT 0- ∞ increased by 2.74 and 3.00 times respectively， t1/2 β increased by 2.75 times，with statistical significance（P＜0.05）. At 30 min after administration ，HCPT nanoparticles and HCPT injection had the highest concentration in lung；with the passage of time ，the drug gradually accumulated in the liver and reached the highest concentration at 60 min. The relative liver uptake rate of HCPT nanoparticles was the highest （6.28）. Taking liver ad target organ ，and the targeting efficiencies of it in heart ，spleen，lung，kindey，brain and plasma were higher than those of HCPT injection. The selectivity index of HCPT nanoparticles in heart ，lung（except for 30 min after administration ），kidney，brain and plasma were significantly higher than those of HCPT injection at 30-120 min after administration. CONCLUSIONS ：HCPT nanoparticles extend the half-life of the drug ， increase its plasma concentration ，and prolong its action time in vivo ，with significant liver targeting. |
| 期刊： | 2021年第32卷第02期 |
| 作者： | 林柳任，窦晨，郑永仁，马云淑，孙赟，程欣 |
| AUTHORS： | LIN Liuren ，DOU Chen，ZHENG Yongren ，MA Yunshu ，SUN Yun，CHENG Xin |
| 关键字： | 羟基喜树碱；纳米粒；药动学；组织分布；靶向性；大鼠 |
| KEYWORDS： | Hydroxycamptothecin；Nanoparticles；Pharmacokinetics；Organization distribution ；Targeting；Rat |
| 阅读数： | 236 次 |
| 本月下载数： | 9 次 |
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