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

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 c...

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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
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cited_by cdi_FETCH-LOGICAL-c435t-7534fa251227fe7af6b6a5e36f9dda5b4a8eaa4ecc6eff941fff4107f833a4813
cites cdi_FETCH-LOGICAL-c435t-7534fa251227fe7af6b6a5e36f9dda5b4a8eaa4ecc6eff941fff4107f833a4813
container_end_page 1585
container_issue 6
container_start_page 1574
container_title Pharmaceutical research
container_volume 30
creator 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
description 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.
doi_str_mv 10.1007/s11095-013-0996-5
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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.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1007/s11095-013-0996-5</identifier><identifier>PMID: 23417512</identifier><identifier>CODEN: PHREEB</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Animals ; Antineoplastic Agents - administration &amp; 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 &amp; 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</subject><ispartof>Pharmaceutical research, 2013-06, Vol.30 (6), p.1574-1585</ispartof><rights>Springer Science+Business Media New York 2013</rights><rights>2014 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c435t-7534fa251227fe7af6b6a5e36f9dda5b4a8eaa4ecc6eff941fff4107f833a4813</citedby><cites>FETCH-LOGICAL-c435t-7534fa251227fe7af6b6a5e36f9dda5b4a8eaa4ecc6eff941fff4107f833a4813</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=27406155$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23417512$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ren, Shu-Ting</creatorcontrib><creatorcontrib>Liao, Yi-Ran</creatorcontrib><creatorcontrib>Kang, Xiao-Ning</creatorcontrib><creatorcontrib>Li, Yi-Ping</creatorcontrib><creatorcontrib>Zhang, Hui</creatorcontrib><creatorcontrib>Ai, Hong</creatorcontrib><creatorcontrib>Sun, Qiang</creatorcontrib><creatorcontrib>Jing, Jing</creatorcontrib><creatorcontrib>Zhao, Xing-Hua</creatorcontrib><creatorcontrib>Tan, Li-Fang</creatorcontrib><creatorcontrib>Shen, Xin-Liang</creatorcontrib><creatorcontrib>Wang, Bing</creatorcontrib><title>The Antitumor Effect of a New Docetaxel-Loaded Microbubble Combined with Low-Frequency Ultrasound In Vitro: Preparation and Parameter Analysis</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><addtitle>Pharm Res</addtitle><description>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.</description><subject>Animals</subject><subject>Antineoplastic Agents - administration &amp; dosage</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antitumor activity</subject><subject>Biochemistry</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering and Bioengineering</subject><subject>Biomedicine</subject><subject>Cancer</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Dogs</subject><subject>Drug delivery systems</subject><subject>Drug Delivery Systems - methods</subject><subject>Drug Stability</subject><subject>Humans</subject><subject>Hydrogen-Ion Concentration</subject><subject>Lipids</subject><subject>Lipids - administration &amp; dosage</subject><subject>Lipids - chemistry</subject><subject>Liver - diagnostic imaging</subject><subject>Liver - drug effects</subject><subject>Medical Law</subject><subject>Medical sciences</subject><subject>Microbubbles - therapeutic use</subject><subject>Multiple tumors. 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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.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>23417512</pmid><doi>10.1007/s11095-013-0996-5</doi><tpages>12</tpages></addata></record>
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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
title The Antitumor Effect of a New Docetaxel-Loaded Microbubble Combined with Low-Frequency Ultrasound In Vitro: Preparation and Parameter Analysis
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