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新型肺靶向多西他赛脂质体在原位肺癌模型兔中的药动学研究
Study on pharmacokinetics of novel lung-targeted Docetaxel liposome in in-situ lung cancer model rabbit
- 中国药房 2023年34卷第15期 页码：1835-1839
- 作者机构：
1.重庆医药高等专科学校药学院/重庆药物制剂工程中心，重庆 401331
2.重庆药友制药有限责任公司，重庆 401121
3.重庆市人民医院药学部，重庆 400014
4.重庆医科大学药学院，重庆 400016
- 作者简介：
副教授，博士。研究方向：药物新剂型与新技术。 E-mail：aywlj@126.com
- 基金信息：重庆市教育委员会科学技术研究项目(KJQN202102805)
DOI：10.6039/j.issn.1001-0408.2023.15.09
中图分类号： R969.1;R944纸质出版日期：2023-08-15，
收稿日期：2023-01-15，
修回日期：2023-06-10，
扫 描 看 全 文
王丽娟,李睿,车坷科等.新型肺靶向多西他赛脂质体在原位肺癌模型兔中的药动学研究 Δ[J].中国药房,2023,34(15):1835-1839.
WANG Lijuan,LI Rui,CHE Keke,et al.Study on pharmacokinetics of novel lung-targeted Docetaxel liposome in in-situ lung cancer model rabbit[J].ZHONGGUO YAOFANG,2023,34(15):1835-1839.
王丽娟,李睿,车坷科等.新型肺靶向多西他赛脂质体在原位肺癌模型兔中的药动学研究 Δ[J].中国药房,2023,34(15):1835-1839. DOI： 10.6039/j.issn.1001-0408.2023.15.09.
WANG Lijuan,LI Rui,CHE Keke,et al.Study on pharmacokinetics of novel lung-targeted Docetaxel liposome in in-situ lung cancer model rabbit[J].ZHONGGUO YAOFANG,2023,34(15):1835-1839. DOI： 10.6039/j.issn.1001-0408.2023.15.09.
摘要
目的
2
研究新型肺靶向多西他赛脂质体（DTX-LP）在原位肺癌模型兔中的药动学行为。
方法
2
采用超高效液相色谱-二级串联质谱（UPLC-MS/MS）法测定DTX在兔血浆中的含量，并进行方法学考察。采用胸腔微创穿刺术制备原位肺癌模型兔，然后随机分为多西他赛注射液（DTX-IN）组和DTX-LP组，耳缘静脉注射给予相应药物，给药剂量均为1.0 mg/kg（以DTX计），然后于5、15、30、60、90、120、240、480 min时取血，测定血浆中DTX浓度。采用DAS 3.3软件进行拟合与分析，并计算药动学参数。
结果
2
本研究所用UPLC-MS/MS法的准确度、精密度良好，符合生物样品分析要求。与DTX-IN组比较，DTX-LP组的药-时曲线趋势较平缓，各时间点的血药浓度更低，
c
max
、
t
1/2
、AUC
0→480 min
、AUC
0→∞
均显著降低（
P
＜0.05）。
结论
2
DTX-LP在血浆中的暴露量较DTX-IN降低，提示其能快速地从体循环中分布到肺靶器官。
Abstract
OBJECTIVE
2
To study the pharmacokinetic behavior of novel lung-targeted Docetaxel liposome （DTX-LP） in in-situ lung cancer model rabbit.
METHODS
2
The content of DTX in rabbit plasma was determined by UPLC-MS/MS， and methodology investigation was conducted. in-situ lung cancer model rabbit was made by the ultra-minimal invasive percutaneous puncture inoculation method. Model rabbits were randomly divided into Docetaxel injection （DTX-IN） group and DTX-LP group. The rabbits were given relevant medicine via ear vein at a dose of 1.0 mg/kg （calculated by DTX）； blood was taken at 5， 15， 30， 60， 90， 120， 240 and 480 minutes to measure the concentration of DTX in plasma. DAS 3.3 software was adopted for fitting and analysis， and to calculate pharmacokinetic parameters.
RESULTS
2
UPLC-MS/MS method used in this study was accurate and precise， which met the requirements of biological sample analysis. Compared with DTX-IN group， drug concentration-time curve of DTX-LP was smoother， the blood concentration at each time point was lower， and
c
max
，
t
1/2
， AUC
0→480 min
and AUC
0→∞
were significantly decreased （
P
＜0.05）.
CONCLUSIONS
2
The drug exposure of DTX-LP in plasma is significantly reduced than DTX-IN， indicating it can be rapidly distributed from systemic circulation to liver target organs.
关键词
多西他赛脂质体原位肺癌模型药动学
Keywords
liposomein-situ lung cancer modelpharmacokinetics
references
SEMB K A，AAMDAL S，OIAN P. Capillary protein leak syndrome appears to explain fluid retention in cancer patients who receive docetaxel treatment[J]. J Clin Oncol，1998，16（10）：3426-3432.
BÉHAR A，PUJADE-LAURAINE E，MAUREL A，et al. The pathophysiological mechanism of fluid retention in advanced cancer patients treated with docetaxel，but not receiving corticosteroid comedication[J]. Br J Clin Pharmacol，1997，43（6）：653-658.
PETROV R A，MEFEDOVA S R，YAMANSAROV E Y，et al. New small-molecule glycoconjugates of docetaxel and GalNAc for targeted delivery to hepatocellular carcinoma[J]. Mol Pharm，2021，18（1）：461-468.
LIU M R，KHAN A R，JI J B，et al. Crosslinked self-assembled nanoparticles for chemo-sonodynamic combination therapy favoring antitumor，antimetastasis management and immune responses[J]. J Control Release，2018，290：150-164.
DU Y Q，TIAN C T，WANG M L，et al. Dipeptide-modified nanoparticles to facilitate oral docetaxel deli- very：new insights into PepT1-mediated targeting strategy[J]. Drug Deliv，2018，25（1）：1403-1413.
YADAV D K，PAWAR H，WANKHADE S，et al. Development of novel docetaxel phospholipid nanoparticles for intravenous administration：quality by design approach[J]. AAPS PharmSciTech，2015，16（4）：855-864.
GU Z L，DA SILVA C G，HAO Y，et al. Effective combination of liposome-targeted chemotherapy and PD-L1 blockade of murine colon cancer[J]. J Control Release，2023，353：490-506.
BRAAL C L，BRUIJN P D，ATRAFI F，et al. A new method for the determination of total and released docetaxel from docetaxel-entrapped core-crosslinked polymeric micelles （CriPec®） by LC-MS/MS and its clinical application in plasma and tissues in patients with various tumours[J]. J Pharm Biomed Anal，2018，161：168-174.
ZHU Y Q，JIANG Y，MENG F H，et al. Highly efficacious and specific anti-glioma chemotherapy by tandem nanomicelles co-functionalized with brain tumor-targeting and cell-penetrating peptides[J]. J Control Release，2018，278：1-8.
SONG C，GAO C，ZHAO J，et al. Construction of long-circulation EpCAM targeted drug delivery system and its application in the diagnosis and treatment of breast cancer[J]. J Biomater Appl，2021，35（8）：947-957.
PALIASHVILI K，POPOV A，KALBER T L，et al. Peritumoral delivery of docetaxel-TIPS microparticles for pro- state cancer adjuvant therapy[J]. Adv Ther，2021，4（2）：2000179.
余瑜，赵领，李伟，等. 注射用肺靶向载药前体脂质体及其使用方法：CN101474155A[P]. 2009-07-08.
余瑜，李伟，刘宇，等. 注射用肺靶向载药前体脂质体及其使用方法：CN200910103135.X [P]. 2009-07-08.
RAROKAR N R，SAOJI S D，RAUT N A，et al. Nanostructured cubosomes in a thermoresponsive depot system：an alternative approach for the controlled delivery of docetaxel[J]. AAPS PharmSciTech，2016，17（2）：436-445.
WANG L J，LI R，CHE K K，et al. Enhanced antitumor effect on intrapulmonary tumors of docetaxel lung-targeted liposomes in a rabbit model of VX2 orthotopic lung cancer[J]. Sci Rep，2017，7（1）：10069.
YANG J，LI X G，LI W J，et al. An improved LC-MS/MS method for determination of docetaxel and its application to population pharmacokinetic study in Chinese cancer patients[J]. Biomed Chromatogr，2020，34（8）：e4857.
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