Name: synthesis of phase-shift nanoemulsions with narrow size distributions for acoustic droplet vaporization and bubble-enhanced ultrasound-mediated ablation
Uploaded: 2012-09-13T12:00:00
Description: Watch this Scientific Journal Video about Synthesis of Phase-shift Nanoemulsions with Narrow Size Distributions for Acoustic Droplet Vaporization and Bubble-enhanced Ultrasound-mediated Ablation at Jo

This work was supported by a BU/CIMIT Applied Healthcare Engineering Predoctoral Fellowship, a National Science Foundation Broadening Participation Research Initiation Grant in Engineering (BRIGE), and the National Institutes of Health (R21EB0094930).

1. Preparation of Phase-shift Nanoemulsion (PSNE)
<ol>
 <li>Dissolve 11 mg DPPC and 1.68 mg DSPE-PEG2000 in chloroform</li>
 <li>Evaporate the organic solvent to form a dry lipid film in a glass round-bottom flask</li>
 <li>Dessicate the lipid film overnight</li>
 <li>Rehydrate the lipid film with 5.5 ml of phosphate-buffered saline (PBS)</li>
 <li>Heat solution in a 45 &deg;C water bath until lipid film dissolves, vortexing periodically</li>
 <li>Transfer lipid solution into 7 ml vial</li>
 <li>So...

<ol>
	<li>Hynynen, K., Darkazanli, A., Unger, E., Schenck, J. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=MRI-guided+noninvasive+ultrasound+surgery.">MRI-guided noninvasive ultrasound surgery.</a> Med. Phys. 20, 107-115 (1993).</li><li>Baban, D. F., Seymour, L. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Control+of+tumour+vascular+permeability.">Control of tumour vascular permeability.</a> Adv. Drug Deliv. Rev. 34, 109-119 (1998).</li><li>Maeda, H., Wu, J., Sawa, T., Matsumura, Y., Hori, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tumor+vascular+permeability+and+the+EPR+effect+in+macromolecular+therapeutics:+a+review.">Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review.</a> J. Control. Release. 65, 271-284 (2000).</li><li>Schadlich, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tumor+accumulation+of+NIR+fluorescent+PEG-PLA+nanoparticles:+impact+of+particle+size+and+human+xenograft+tumor+model.">Tumor accumulation of NIR fluorescent PEG-PLA nanoparticles: impact of particle size and human xenograft tumor model.</a> ACS Nano. 5, 8710-8720 (2011).</li><li>Williams, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Convertible+perfluorocarbon+droplets+for+cancer+detection+and+therapy.">Convertible perfluorocarbon droplets for cancer detection and therapy.</a> 2010 IEEE Ultrasonics Symposium. , (2010).</li><li>Martz, T. D., Sheeran, P. S., Bardin, D., Lee, A. P., Dayton, P. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Precision+manufacture+of+phase-change+perfluorocarbon+droplets+using+microfluidics.">Precision manufacture of phase-change perfluorocarbon droplets using microfluidics.</a> Ultrasound Med. Biol. 37, 1952-1957 (2011).</li><li>Giesecke, T., Hynynen, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasound-mediated+cavitation+thresholds+of+liquid+perfluorocarbon+droplets+in+vitro.">Ultrasound-mediated cavitation thresholds of liquid perfluorocarbon droplets in vitro.</a> Ultrasound Med. Biol. 29, 1359-1365 (2003).</li><li>Sheeran, P. S., Luois, S., Dayton, P. A., Matsunaga, T. O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Formulation+and+Acoustic+Studies+of+a+New+Phase-Shift+Agent+for+Diagnostic+and+Therapeutic+Ultrasound.">Formulation and Acoustic Studies of a New Phase-Shift Agent for Diagnostic and Therapeutic Ultrasound.</a> Langmuir. 27, 10412-10420 (2011).</li><li>Sheeran, P. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Decafluorobutane+as+a+phase-change+contrast+agent+for+low-energy+extravascular+ultrasonic+imaging.">Decafluorobutane as a phase-change contrast agent for low-energy extravascular ultrasonic imaging.</a> Ultrasound Med. Biol. 37, 1518-1530 (2011).</li><li>Zhang, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> The Application of Phase-Shift Nanoemulsion in High Intensity Focused Ultrasound: An In Vitro Study [Doctoral Dissertation]. , (2011).</li><li>Allen, T. M., Hansen, C., Martin, F., Redemann, C., Yau-Young, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Liposomes+containing+synthetic+lipid+derivatives+of+poly(ethylene+glycol)+show+prolonged+circulation+half-lives+in+vivo.">Liposomes containing synthetic lipid derivatives of poly(ethylene glycol) show prolonged circulation half-lives in vivo.</a> Biochim. Biophys. Acta. 1066, 29-36 (1991).</li><li>Klibanov, A. L., Maruyama, K., Beckerleg, A. M., Torchilin, V. P., Huang, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Activity+of+amphipathic+poly(ethylene+glycol)+5000+to+prolong+the+circulation+time+of+liposomes+depends+on+the+liposome+size+and+is+unfavorable+for+immunoliposome+binding+to+target.">Activity of amphipathic poly(ethylene glycol) 5000 to prolong the circulation time of liposomes depends on the liposome size and is unfavorable for immunoliposome binding to target.</a> Biochim. Biophys. Acta. 1062, 142-148 (1991).</li><li>Klibanov, A. L., Maryama, K., Torchilin, V. P., Huang, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Amphipathic+polyethyleneglycols+effectively+prolong+the+circulation+time+of+liposomes.">Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes.</a> FEBS Lett. 268, 235-237 (1990).</li><li>Gabizon, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prolonged+circulation+time+and+enhanced+accumulation+in+malignant+exudates+of+Doxorubicin+encapsulated+in+polyethylene-glycol+coated+liposomes.">Prolonged circulation time and enhanced accumulation in malignant exudates of Doxorubicin encapsulated in polyethylene-glycol coated liposomes.</a> Cancer Res. 54, 987-992 (1994).</li><li>Awasthi, V. D., Garcia, D., Goins, B. A., Philips, W. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Circulation+and+biodistribution+profiles+of+long-circulating+PEG-liposomes+of+various+sizes+in+rabbits.">Circulation and biodistribution profiles of long-circulating PEG-liposomes of various sizes in rabbits.</a> Int. J. Pharm. 253, 121-132 (2003).</li><li>Zhang, P., Porter, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+in+vitro+study+of+a+phase-shift+nanoemulsion:+a+potential+nucleation+agent+for+bubble-enhanced+HIFU+tumor+ablation.">An in vitro study of a phase-shift nanoemulsion: a potential nucleation agent for bubble-enhanced HIFU tumor ablation.</a> Ultrasound Med. Biol. 36, 1856-1866 (2010).</li><li>Lafon, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gel+phantom+for+use+in+high-intensity+focused+ultrasound+dosimetry.">Gel phantom for use in high-intensity focused ultrasound dosimetry.</a> Ultrasound Med. Biol. 31, 1383-1389 (2005).</li></ol>

High-intensity focused ultrasound (HIFU) is used clinically to thermally ablate tumors.1 To enhance localized heating and improve thermal ablation in tumors, lipid-coated perfluorocarbon droplets have been developed which can be vaporized by HIFU. The vasculature in many tumors is abnormally leaky due to their rapid growth.2 Thus, nanoparticles are able to penetrate the fenestrations and passively accumulate within tumors, a process known as the enhanced permeability and retention (EPR) effect...

<table border="1">
 <tbody>
 <tr>
 <td>Common Name</td>
 <td>Manufacturer</td>
 <td>Cat. Number</td>
 <td>Full Name / Description</td>
 </tr>
 <tr>
 <td>DPPC</td>
 <td>Avanti Lipids, Alabaster, AL, USA</td>
 <td>850355P</td>
 <td>1,2-dipalmitoyl-sn-glycero-3-phosphocholine</td>
 </tr>
 <tr>
 <td>DSPE-PEG2000</td>
 <td>Avanti Lipids, Alabaster, AL, USA</td>
 <td>880120P</td>
 <td>1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (ammonium salt)</td>
 </tr>
 <tr>
 <td>DDFP</td>
 <td>Fluoromed, Round Rock, TX, USA</td>
 <td>CAS: 138495-42-8</td>
 <td>Dodecafluoropentane (C5F12)</td>
 </tr>
 <tr>
 <td>PBS</td>
 <td>Sigma-Aldrich, St. Louis, MO, USA</td>
 <td>P2194</td>
 <td>Phosphate-buffered saline</td>
 </tr>
 <tr>
 <td>Chloroform</td>
 <td>Sigma-Aldrich, St. Louis, MO, USA</td>
 <td>372978</td>
 <td>Chloroform</td>
 </tr>
 <tr>
 <td>Acrylamide</td>
 <td>Sigma-Aldrich, St. Louis, MO, USA</td>
 <td>A9926</td>
 <td>40% 19:1 acrylamide/bis-acrylamide</td>
 </tr>
 <tr>
 <td>Tris buffer</td>
 <td>Sigma-Aldrich, St. Louis, MO, USA</td>
 <td>T2694</td>
 <td>1M, pH 8, trizma hydrochloride and trizma base</td>
 </tr>
 <tr>
 <td>BSA</td>
 <td>Sigma-Aldrich, St. Louis, MO, USA</td>
 <td>A3059</td>
 <td>Bovine serum albumin</td>
 </tr>
 <tr>
 <td>APS</td>
 <td>Sigma-Aldrich, St. Louis, MO, USA</td>
 <td>A3678</td>
 <td>Ammonium persulfate solution</td>
 </tr>
 <tr>
 <td>TEMED</td>
 <td>Sigma-Aldrich, St. Louis, MO, USA</td>
 <td>87689</td>
 <td>N,N,N',N'-Tetramethylethylenediamine</td>
 </tr>
 <tr>
 <td>&nbsp;</td>
 <td>&nbsp;</td>
 <td>&nbsp;</td>
 <td>Equipment</td>
 </tr>
 <tr>
 <td>Sonicator (3 mm tip)</td>
 <td>Sonics &amp; Materials, Inc., Newtown, CT, USA</td>
 <td>Vibra-Cell</td>
 <td></td>
 </tr>
 <tr>
 <td>Water bath</td>
 <td>Thermo Fisher Scientific, Waltham, MA, USA</td>
 <td>Neslab EX-7</td>
 <td></td>
 </tr>
 <tr>
 <td>Extruder</td>
 <td>Northern Lipids, Burnaby, BC, Canada</td>
 <td>LIPEX</td>
 <td></td>
 </tr>
 <tr>
 <td>Extruder Filters</td>
 <td>Whatman, Piscataway, NJ, USA </td>
 <td>Nuclepore #110605 and #110606</td>
 <td></td>
 </tr>
 <tr>
 <td>Extruder Drain Disc</td>
 <td>Sterlitech Corporation, Kent, WA, USA</td>
 <td>#PETEDD25100</td>
 <td></td>
 </tr>
 <tr>
 <td>Plastic chamber</td>
 <td>U.S. Plastic Corporation, Lima, OH, USA</td>
 <td>#55288, 1 3/16"x1 3/16"x2 7/16"</td>
 <td></td>
 </tr>
 </tbody>
</table>

synthesis of phase-shift nanoemulsions with narrow size distributions for acoustic droplet vaporization and bubble-enhanced ultrasound-mediated ablation

High-intensity focused ultrasound (HIFU) is used clinically to thermally ablate tumors. To enhance localized heating and improve thermal ablation in tumors, lipid-coated perfluorocarbon droplets have been developed which can be vaporized by HIFU. The vasculature in many tumors is abnormally leaky due to their rapid growth, and nanoparticles are able to penetrate the fenestrations and passively accumulate within tumors. Thus, controlling the size of the droplets can result in better accumulation within tumors. In this report, the preparation of stable droplets in a phase-shift nanoemulsion (PSNE) with a narrow size distribution is described. PSNE were synthesized by sonicating a lipid solution in the presence of liquid perfluorocarbon. A narrow size distribution was obtained by extruding the PSNE multiple times using filters with pore sizes of 100 or 200 nm. The size distribution was measured over a 7-day period using dynamic light scattering. Polyacrylamide hydrogels containing PSNE were prepared for in vitro experiments. PSNE droplets in the hydrogels were vaporized with ultrasound and the resulting bubbles enhanced localized heating. Vaporized PSNE enables more rapid heating and also reduces the ultrasound intensity needed for thermal ablation. Thus, PSNE is expected to enhance thermal ablation in tumors, potentially improving therapeutic outcomes of HIFU-mediated thermal ablation treatments.

Watch this Scientific Journal Video about Synthesis of Phase-shift Nanoemulsions with Narrow Size Distributions for Acoustic Droplet Vaporization and Bubble-enhanced Ultrasound-mediated Ablation at Jo

Synthesis of Phase-shift Nanoemulsions with Narrow Size Distributions for Acoustic Droplet Vaporization and Bubble-enhanced Ultrasound-mediated Ablation

Phase-shift nanoemulsions (PSNE) can be vaporized using high intensity focused ultrasound to enhance localized heating and improve thermal ablation in tumors. In this report, the preparation of stable PSNE with a narrow size distribution is described. Furthermore, the impact of vaporized PSNE on ultrasound-mediated ablation is demonstrated in tissue-mimicking phantoms.

High-intensity  focused ultrasound (HIFU) is used clinically to thermally ablate tumors. To  enhance localized heating and improve thermal ablation in ...

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