多西紫杉醇纳米胶束在小鼠体内的药代动力学及其肿瘤组织分布

王杰; 王亚杰; 郝单丽; 臧琛; 易红; 德格晶; 陈燕军

doi:10.13422/j.cnki.syfjx.20182310

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多西紫杉醇纳米胶束在小鼠体内的药代动力学及其肿瘤组织分布

药物代谢 | 更新时间：2021-02-09

- 多西紫杉醇纳米胶束在小鼠体内的药代动力学及其肿瘤组织分布
- Pharmacokinetics and Tumor Tissue Distribution of Docetaxel Nanomicelles in Mice
- 中国实验方剂学杂志 2019年25卷第7期页码：140-145
- 作者机构：
  
  中国中医科学院　中药研究所，北京　 100700
- 作者简介：
  
  王杰，硕士，从事中药药剂研究，Tel：010-84036059，E-mail：zyswangjie@163.com
  陈燕军，博士，研究员，从事中药新型给药系统的研究，Tel：010-84036059，E-mail:yjchen@icmm.ac.cn
- 基金信息：
  
  国家重点基础研究发展计划（973计划）(2014CB543003)
- DOI：10.13422/j.cnki.syfjx.20182310
  中图分类号： R22;R283.6;R969.1;R94;R285.5
- 收稿日期：2018-04-09，
  
  网络出版日期：2018-09-12，
  
  纸质出版日期：2019-04-05
- 稿件说明：
移动端阅览
王杰, 王亚杰, 郝单丽, 等. 多西紫杉醇纳米胶束在小鼠体内的药代动力学及其肿瘤组织分布[J]. 中国实验方剂学杂志, 2019,25(7):140-145.

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.
王杰, 王亚杰, 郝单丽, 等. 多西紫杉醇纳米胶束在小鼠体内的药代动力学及其肿瘤组织分布[J]. 中国实验方剂学杂志, 2019,25(7):140-145. DOI： 10.13422/j.cnki.syfjx.20182310.

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

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