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Improved anti-tumor efficiency against prostate cancer by docetaxel-loaded PEG-PCL micelles.

作者信息

Jin Ming-Ji, Piao Sheng-Jun, Jin Tie-Xiong, Jin Zhe-Hu, Yin Xue-Zhe, Gao Zhong-Gao

机构信息

State Key Laboratory of Bioactive Substance and Functions of Natural Medicines, Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.

Yanbian University Hospital, Yanji, 133000, China.

出版信息

J Huazhong Univ Sci Technolog Med Sci. 2014 Feb;34(1):66-75. doi: 10.1007/s11596-014-1233-0. Epub 2014 Feb 6.


DOI:10.1007/s11596-014-1233-0
PMID:24496681
Abstract

This study primarily focused on the systematic assessment of both in vitro and in vivo anti-tumor effects of docetaxel-loaded polyethylene glycol (PEG)2000-polycaprolactone (PCL)2600 micelles on hormone-refractory prostate cancer (HRPC). By using solvent evaporation method, PEG-PCL was chosen to prepare doxetaxel (DTX)-loaded mPEG-PCL micelles (DTX-PMs), with the purpose of eliminating side effects of the commercial formulation (Tween 80) and prolonging the blood circulation time. The prepared DTX-PMs had an average particle size of 25.19±2.36 nm, a zeta potential of 0.64±0.15 mV, a polydispersity index of 0.56±0.03, a drug loading of (8.72±1.05)%, and an encapsulation efficiency of (98.1±8.4)%. In vitro cytotoxicity studies indicated that DTX-PMs could effectively kill LNCap-C4-2B cells and show a dose- and time-dependent efficacy. The hemolysis test showed that DTX-PMs had less hemocytolysis than the commercial product of Duopafei®. A sustained in vitro release behavior and prolonged circulation time in blood vessels were observed in the DTX-PMs. Furthermore, when compared with Duopafei®, the DTX-PMs dramatically reduced the prostate specific antigen (PSA) level and tumor growth of prostate tumor-bearing nude mice in vivo. In conclusion, the DTX-PMs can lower systemic side effects, improve anti-tumor activity with prolonged blood circulation time, and will bring an alternative to patients with HRPC.

摘要

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本文引用的文献

[1]
Docetaxel chemotherapy for Chinese patients with castrate-resistant prostate cancer.

Hong Kong Med J. 2013-4-3

[2]
Update on taxane development: new analogs and new formulations.

Drug Des Devel Ther. 2012

[3]
Tissue distribution and pharmacokinetics evaluation of DOMC-FA micelles for intravenous delivery of PTX.

J Drug Target. 2012-10-9

[4]
Improving anti-tumor activity with polymeric micelles entrapping paclitaxel in pulmonary carcinoma.

Nanoscale. 2012-8-22

[5]
Enhanced antitumor efficacy, biodistribution and penetration of docetaxel-loaded biodegradable nanoparticles.

Int J Pharm. 2012-4-12

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Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size.

Nat Nanotechnol. 2011-10-23

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Urol Oncol. 2011-10-19

[8]
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J Control Release. 2011-6-24

[9]
Role of cellular uptake in the reversal of multidrug resistance by PEG-b-PLA polymeric micelles.

Biomaterials. 2011-5-4

[10]
Preparation, characterization and evaluation of docetaxel-loaded, folate-conjugated PEG-liposomes.

Yakugaku Zasshi. 2010-10

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