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Pharmaceutical Research

, Volume 30, Issue 6, pp 1574–1585 | Cite as

The Antitumor Effect of a New Docetaxel-Loaded Microbubble Combined with Low-Frequency Ultrasound In Vitro: Preparation and Parameter Analysis

  • Shu-Ting Ren
  • Yi-Ran Liao
  • Xiao-Ning Kang
  • Yi-Ping Li
  • Hui Zhang
  • Hong Ai
  • Qiang Sun
  • Jing Jing
  • Xing-Hua Zhao
  • Li-Fang Tan
  • Xin-Liang Shen
  • Bing Wang
Research Paper

Abstract

Purpose

To develop a novel docetaxel (DOC)-loaded lipid microbubbles (MBs) for achieving target therapy and overcoming the poor water-solubility drawback of DOC.

Methods

A novel DOC-loaded microbubble (DOC + MB) was prepared by lyophilization and the physicochemical properties including ultrasound contrast imaging of the liver were measured. The anti-tumor effect of the DOC + MBs combined with low-frequency ultrasound (LFUS; 0.8Hz, 2.56 W/cm2, 50% cycle duty) on the DLD-1 cancer cell line was examined using an MTT assay.

Results

The physicochemical properties of the two tested formats of DOC + MBs (1.0 mg and 1.6 mg) was shown: concentration, (6.74 ± 0.02) × 108 bubbles/mL and (8.27 ± 0.15) × 108 bubbles/mL; mean size, 3.296 ± 0.004 μm and 3.387 ± 0.005 μm; pH value, 6.67 ± 0.11 and 6.56 ± 0.05; release rate, 3.41% and 12.50%; Zeta potential, −37.95 ± 7.84 mV and −44.35 ± 8.70 mV; and encapsulation efficiency, 54.9 ± 6.21% and 46.3 ± 5.69%, respectively. Compared with SonoVue, the DOC + MBs similarly enhanced the echo signal of the liver imaging. The anti-tumor effect of the DOC + MBs/LFUS group was significantly better than that of DOC alone and that of the normal MBs/LFUS groups.

Conclusions

The self-made DOC + MBs have potential as a new ultrasound contrast agent and drug-loaded microbubble, and can obviously enhance the antitumor effect of DOC under LFUS exposure.

Key words

docetaxel lipid microbubbles tumor-targeted therapy ultrasound contrast agent 

Abbreviations

DOC

docetaxel

DOC + MB

docetaxel-loaded microbubble

IR

inhibitory rate

LFUS

low-frequency ultrasound

MB

microbubble

NMB

normal microbubble

NS

normal saline

PTX

paclitaxel

PBS

phosphate buffer saline

RP-HPLC

reverse-phase liquid chromatography

TtoPk

time to peak

TIC

time intensity curve

UCA

ultrasound contrast agent

US

ultrasound

Notes

Acknowledgments and Disclosures

The authors would like to thank Hua-Sheng Liu, Ph.D. and Jiang-Wei Liang for helps in the experiment. The present study was supported by the Scientific Technology Planning Foundation of Shaanxi Province (No.2010K12-01, 2011K12-56), Province Ministry Graveness Engineering Program (No.2009ZDKG-20; No.2008ZDKG-60, 2007ZDKG-290).

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Shu-Ting Ren
    • 1
  • Yi-Ran Liao
    • 2
  • Xiao-Ning Kang
    • 1
  • Yi-Ping Li
    • 2
  • Hui Zhang
    • 2
  • Hong Ai
    • 3
  • Qiang Sun
    • 2
  • Jing Jing
    • 1
  • Xing-Hua Zhao
    • 2
  • Li-Fang Tan
    • 3
  • Xin-Liang Shen
    • 4
  • Bing Wang
    • 1
  1. 1.Department of Pathology and Therapeutic Vaccines Engineering Center of Shaanxi Province, School of MedicineXi’an Jiaotong UniversityXi’anChina
  2. 2.Department of Pharmacology and Therapeutic Vaccines Engineering Center of Shaanxi Province, School of MedicineXi’an Jiaotong UniversityXi’anChina
  3. 3.Department of Ultrasound Imaging, First Affiliated Hospital of Medical CollegeXi’an Jiaotong UniversityXi’anChina
  4. 4.China National Biotechnology GroupBeijingChina

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