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

• Published in: Pharmaceutical research 2013-06, Vol.30 (6), p.1574-1585
• Main Authors: Ren, Shu-Ting, Liao, Yi-Ran, Kang, Xiao-Ning, Li, Yi-Ping, Zhang, Hui, Ai, Hong, Sun, Qiang, Jing, Jing, Zhao, Xing-Hua, Tan, Li-Fang, Shen, Xin-Liang, Wang, Bing
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antitumor activity; Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Cancer; Cell Line, Tumor; Cell Proliferation - drug effects; Dogs; Drug delivery systems; Drug Delivery Systems - methods; Drug Stability; Humans; Hydrogen-Ion Concentration; Lipids; Lipids - administration & dosage; Lipids - chemistry; Liver - diagnostic imaging; Liver - drug effects; Medical Law; Medical sciences; Microbubbles - therapeutic use; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Pharmaceutical sciences; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Research Paper; Solubility; Taxoids - chemistry; Taxoids - therapeutic use; Tumors; Ultrasonic imaging; Ultrasonics - methods; Ultrasonography; Water - chemistry
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-013-0996-5

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/cm 2 , 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) × 10 8 bubbles/mL and (8.27 ± 0.15) × 10 8 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.