Back to Journals » International Journal of Nanomedicine » Volume 8 » Issue 1

Antitumor activity of docetaxel-loaded polymeric nanoparticles fabricated by Shirasu porous glass membrane-emulsification technique

Authors Yu YN, Tan SW, Zhao S, Zhuang XT, Song QL, Wang YL, Zhou Q, Zhang ZP

Received 14 May 2013

Accepted for publication 8 June 2013

Published 29 July 2013 Volume 2013:8(1) Pages 2641—2652

DOI https://doi.org/10.2147/IJN.S48214

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Yunni Yu,1,* Songwei Tan,1,2,* Shuang Zhao,1 Xiangting Zhuang,1 Qingle Song,1 Yuliang Wang,1 Qin Zhou,2,3 Zhiping Zhang1,2

1Tongji School of Pharmacy, 2National Engineering Research Center for Nanomedicine, 3College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People’s Republic of China

*These authors contributed equally to this work

Abstract: Docetaxel (DTX) has excellent efficiency against a wide spectrum of cancers. However, the current clinical formulation has limited its usage, as it causes some severe side effects. Various polymeric nanoparticles have thus been developed as alternative formulations of DTX, but they have been mostly fabricated on a laboratory scale. Previously, we synthesized a novel copolymer, poly(lactide)-D-α-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS), and found that it exhibited great potential in drug delivery with improved properties. In this study, we applied the Shirasu porous glass (SPG) membrane-emulsification technique to prepare the DTX-loaded PLA-TPGS nanoparticles on a pilot scale. The effect of several formulation variables on the DTX-loaded nanoparticle properties, including particle size, zeta potential, and drug-encapsulation efficiency, were investigated based on surfactant type and concentration in the aqueous phase, organic/aqueous phase volumetric ratio, membrane-pore size, transmembrane cycles, and operation pressure. The DTX-loaded nanoparticles were obtained with sizes of 306.8 ± 5.5 nm and 334.1 ± 2.7 nm (mean value ± standard deviation), and drug-encapsulation efficiency of 81.8% ± 4.5% and 64.5% ± 2.7% for PLA-TPGS and poly(lactic-co-glycolic acid) (PLGA) nanoparticles, respectively. In vivo pharmacokinetic study exhibited a significant advantage of PLA-TPGS nanoparticles over PLGA nanoparticles and Taxotere. Drug-loaded PLA-TPGS nanoparticles exhibited 1.78-, 6.34- and 3.35-fold higher values for area under the curve, half-life, and mean residence time, respectively, compared with those of PLGA nanoparticles, and 2.23-, 13.2-, 8.51-fold higher than those of Taxotere, respectively. In vivo real-time distribution of nanoparticles was measured on tumor-bearing mice by near-infrared fluorescence imaging, which demonstrated that the PLA-TPGS nanoparticles achieved much higher concentration and longer retention in tumors than PLGA nanoparticles after intravenous injection. This is consistent with the pharmacokinetic behavior of the nanoparticles. The tumor-inhibitory effect of DTX-loaded nanoparticles was observed in vivo in an H22 tumor-bearing mice model via intravenous administration. This indicated that PLA-TPGS nanoparticles are a feasible drug-delivery formulation with a pilot fabrication technique and have superior pharmacokinetic and anticancer effects compared to the commercially available Taxotere.

Keywords: SPG membrane emulsification, nanoparticles, docetaxel, pharmacokinetics, antitumor activity

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Other article by this author:

D-α-tocopherol polyethylene glycol succinate-based derivative nanoparticles as a novel carrier for paclitaxel delivery

Wu YP, Chu Q, Tan SW, Zhuang XT, Bao YL, Wu TT, Zhang ZP

International Journal of Nanomedicine 2015, 10:5219-5235

Published Date: 20 August 2015

Readers of this article also read:

Molecular targets in arthritis and recent trends in nanotherapy

Roy K, Kanwar RK, Kanwar JR

International Journal of Nanomedicine 2015, 10:5407-5420

Published Date: 26 August 2015

Is increasing the dose of Entecavir effective in partial virological responders?

Erturk A, Adnan Akdogan R, Parlak E, Cure E, Cumhur Cure M, Ozturk C

Drug Design, Development and Therapy 2014, 8:621-625

Published Date: 29 May 2014

Vincristine sulfate liposomal injection for acute lymphoblastic leukemia

Soosay Raj TA, Smith AM, Moore AS

International Journal of Nanomedicine 2013, 8:4361-4369

Published Date: 6 November 2013

Photodynamic therapy of a 2-methoxyestradiol tumor-targeting drug delivery system mediated by Asn-Gly-Arg in breast cancer

Shi J, Wang Z, Wang L, Wang H, Li L, Yu X, Zhang J, Ma R, Zhang Z

International Journal of Nanomedicine 2013, 8:1551-1562

Published Date: 19 April 2013

Controlled-release approaches towards the chemotherapy of tuberculosis

Saifullah B, Hussein MZ, Hussein Al Ali SH

International Journal of Nanomedicine 2012, 7:5451-5463

Published Date: 12 October 2012