Pharmacokinetics and Tumor Tissue Distribution of Docetaxel Nanomicelles in Mice
10.13422/j.cnki.syfjx.20182310
- VernacularTitle: 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
- Author:
Jie WANG
1
;
Ya-jie WANG
1
;
Dan-li HAO
1
;
Chen ZANG
1
;
Hong YI
1
;
Ge-jing DE
1
;
Yan-jun CHEN
1
Author Information
1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
- Publication Type:Research Article
- Keywords:
docetaxel;
pH-sensitive drug-loaded micelles;
pharmacokinetics;
tissue distribution;
paclitaxel;
tumor tissue;
tail intravenous injection
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2019;25(7):140-145
- CountryChina
- Language:Chinese
-
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(AUC0-∞) 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.
