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