Pharmacokinetics and Tumor Tissue Distribution of Docetaxel Nanomicelles in Mice

Jie WANG; Ya-jie WANG; Dan-li HAO; Chen ZANG; Hong YI; Ge-jing DE; Yan-jun CHEN

doi:10.13422/j.cnki.syfjx.20182310

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Pharmacokinetics and Tumor Tissue Distribution of Docetaxel Nanomicelles in Mice

Drug Metabolism | 更新时间：2021-02-09

- Pharmacokinetics and Tumor Tissue Distribution of Docetaxel Nanomicelles in Mice
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 7, Pages: 140-145(2019)
- 作者机构：
  
  中国中医科学院　中药研究所，北京　 100700
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20182310
  CLC： R22;R283.6;R969.1;R94;R285.5
- Received：09 April 2018，
  
  Published Online：12 September 2018，
  
  Published：05 April 2019
- 稿件说明：
移动端阅览
Jie WANG, Ya-jie WANG, Dan-li HAO, et al. Pharmacokinetics and Tumor Tissue Distribution of Docetaxel Nanomicelles in Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(7): 140-145.
DOI：

Jie WANG, Ya-jie WANG, Dan-li HAO, et al. Pharmacokinetics and Tumor Tissue Distribution of Docetaxel Nanomicelles in Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(7): 140-145. DOI： 10.13422/j.cnki.syfjx.20182310.

摘要

目的：

探究多西紫杉醇纳米胶束的药代动力学及其在肿瘤组织中的分布情况。

方法：

采用薄膜水化法制备多西紫杉醇纳米胶束；利用HPLC建立多西紫杉醇(DTX)在生物样品中的含量测定方法并进行相应的方法学评价；建立小鼠Lewis肺癌模型，利用尾静脉注射给药方式分别考察游离药物(DTX)，非pH敏感性载药胶束(PELA-DTX)，pH敏感性载药胶束(PBAE-DTX)在给药剂量为20 mg·kg

－1

时，对荷瘤小鼠药代动力学及组织分布的影响。

结果：

成功制备了多西紫杉醇纳米胶束PELA-DTX与PBAE-DTX；采用HPLC建立了多西紫杉醇在小鼠体内的含量测定方法，且该方法的线性关系、精密度、回收率均符合要求。PBAE-DTX的血药浓度在24 h内一直处于较高的水平。与PELA-DTX，DTX相比，PBAE-DTX的药时曲线下面积（AUC

0-∞

）分别增大3.63%，8.96%，平均驻留时间（MRT）分别延长了2.86%和6.43%，半衰期延长，药物血液循环时间延长。给药后1 h内，3种多西紫杉醇制剂在心、肝、脾、肺、肾及肿瘤组织中均有分布，随时间延长，分布降低，且24 h时PBAE-DTX在肿瘤组织中的分布显著高于PELA-DTX和DTX。

结论：

PBAE-DTX能够延长多西紫杉醇在血液中的循环时间，提高其生物利用度及在肿瘤组织的分布程度。

Abstract

Objective:

To investigate the pharmacokinetics and the distribution in tumor tissues of docetaxel nanomicelles.

Method:

The docetaxel nanomicelles was prepared by filming-rehydration method.HPLC was employed to determine the content of docetaxel in biological samples and the corresponding methodological evaluation was carried out.The mouse Lewis lung carcinoma model was established

when dosage of administration in tail vein was 20 mg·kg

-1

and then the effect of free drug(DTX)

non-pH-sensitive drug-loaded micelles(PELA-DTX) and pH-sensitive drug-loaded micelles(PBAE-DTX) on the pharmacokinetics and tissue distribution of tumor-bearing mice were investigated.

Result:

The docetaxel nanomicelles(PELA-DTX and PBAE-DTX) were successfully prepared.The method for the determination of docetaxel in mice was established by HPLC

the linearity

precision of the method and the recovery rate of samples all met the requirements.In the pharmacokinetic study

the plasma concentration of PBAE-DTX was always at a high level within 24 h. Compared with PELA-DTX and DTX

the areas under the curve(AUC

0-∞

) of PBAE-DTX were increased by 3.63% and 8.96%

the mean residence times(MRT) were extended by 2.86% and 6.43%

the half-life and the drug blood circulation time were prolonged.In the tissue distribution study

it was found that three docetaxel preparations were distributed in the heart

liver

spleen

lung

kidney and tumor tissue within 1 h after administration

but the distribution of these drugs in the tissues was reduced along with the extension of time

the accumulation of PBAE-DTX in tumor tissue was significantly higher than that in DTX and PELA-DTX at 24 h.

Conclusion:

PBAE-DTX can prolong the circulation time of docetaxel in the blood

increase its bioavailability

and significantly increase its distribution in tumor tissue.

关键词

Keywords

references

HE X , LI C , WU X , et al . Docetaxel inhibits the proliferation of non-small-cell lung cancer cells via upregulation of microRNA-7 expression [J]. Int J Clin Exp Pathol , 2015 , 8 ( 8 ): 9072 - 9080 .

LI Y , JIN M , SHAO S , et al . Small-sized polymeric micelles incorporating docetaxel suppress distant metastases in the clinically-relevant 4T1 mouse breast cancer model [J]. BMC Cancer , 2014 , doi: 10.1186/1471-2407-14-329 doi:10.1186/1471-2407-14-329 .

LIU E , LIU Z , ZHOU Y. Carboplatin-docetaxel-induced activity against ovarian cancer is dependent on up-regulated lncRNA PVT1 [J]. Int J Clin Exp Pathol , 2015 , 8 ( 4 ): 3803 - 3810 .

XIAO P , MA T , ZHOU C , et al . Anticancer effect of docetaxel induces apoptosis of prostate cancer via the cofilin-1 and paxillin signaling pathway [J]. Mol Med Rep , 2016 , 13 ( 5 ): 4079 - 4084 .

Di Lauro L , Vici P , Belli F , et al . Docetaxel，oxaliplatin，and capecitabine combination chemotherapy for metastatic gastric cancer [J]. Gastric Cancer , 2014 , 17 ( 4 ): 718 - 724 .

曹熙．多西紫杉醇聚合物胶束的研究进展 [J]. 中国新药杂志， 2017 , 26 ( 10 ): 1137 - 1143 .

季冬英，吴琼珠，平其能． PLA-mPEG的合成和多西紫杉醇聚合物胶束的制备 [J]. 中国药科大学学报， 2008 , 39 ( 3 ): 223 - 227 .

吴秋澜，栾立标 . 7-乙基-10-羟基喜树碱两亲性嵌段共聚物亚微粒的制备及性质 [J]. 药学学报， 2007 , 42 ( 4 ): 440 - 444 .

杜林娇，岳巧欣，李真真，等．紫杉醇聚合物胶束的制备及其pH响应性能 [J]. 中国实验方剂学杂志， 2015 , 21 ( 10 ): 9 - 12 .

岳巧欣，杜林娇，李真真，等．载紫杉醇的聚乙二醇-聚乳酸-聚- β -氨基酯纳米胶束药动学及其在小鼠体内分布研究 [J]. 中国新药杂志， 2016 , 25 ( 8 ): 933 - 937 .

SONG W , TANG Z , LI M , et al . Tunable pH-sensitive poly( β -amino ester)s synthesized from primary amines and diacrylates for intracellular drug delivery [J]. Macromol Biosci , 2012 , 12 ( 10 ): 1375 - 1383 .

刘馨，伍治平，左曙光，等．小鼠Lewis肺癌原位模型的构建 [J]. 中国肺癌杂志， 2010 , 13 ( 1 ): 42 - 47 .

王熙才，邓意辉，王绍宁，等． RP-HPLC法测定多西紫杉醇脂质体药物含量 [J]. 中国药剂学杂志：网络版， 2003 , 1 ( 3 ): 115 - 118 .

CHEN F Q , ZHANG J M , WANG L , et al . Tumor pH e -triggered charge-reversal and redox-responsive nanoparticles for docetaxel delivery in hepatocellular carcinoma treatment [J]. Nanoscale , 2015 , 7 ( 38 ): 15763 - 15779 .

张祚德，王安元，郝建冬，等．二氢卟吩e6脂质体在荷瘤小鼠体内的药动学及靶向性分析 [J]. 中国实验方剂学杂志， 2018 , 24 ( 13 ): 71 - 77 .

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