Microbubble Compositions, Properties and Biomedical Applications.

Over the last decade, there has been significant progress towards the development of microbubbles as theranostics for a wide variety of biomedical applications. The unique ability of microbubbles to respond to ultrasound makes them useful agents for contrast ultrasound imaging, molecular imaging, and targeted drug and gene delivery. The general composition of a microbubble is a gas core stabilized by a shell comprised of proteins, lipids or polymers. Each type of microbubble has its own unique advantages and can be tailored for specialized functions. In this review, different microbubbles compositions and physiochemical properties are discussed in the context of current progress towards developing novel constructs for biomedical applications, with specific emphasis on molecular imaging and targeted drug/gene delivery.

[1]  H. Stone,et al.  Interfacial Polygonal Nanopatterning of Stable Microbubbles , 2008, Science.

[2]  Gaio Paradossi,et al.  Stable polymeric microballoons as multifunctional device for biomedical uses: synthesis and characterization. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[3]  David Needham,et al.  Test of the Epstein-Plesset model for gas microparticle dissolution in aqueous media: effect of surface tension and gas undersaturation in solution. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[4]  K. Bjerknes,et al.  Air-filled polymeric microcapsules from emulsions containing different organic phases. , 2001, Journal of microencapsulation.

[5]  Paul A Dayton,et al.  A stimulus-responsive contrast agent for ultrasound molecular imaging. , 2008, Biomaterials.

[6]  E. Unger,et al.  Local drug and gene delivery through microbubbles. , 2001, Progress in cardiovascular diseases.

[7]  S. Kaul,et al.  Delivery of Drugs with Ultrasound , 2001, Echocardiography.

[8]  R. Busse,et al.  Vascular Gene Transfer of Phosphomimetic Endothelial Nitric Oxide Synthase (S1177D) Using Ultrasound-Enhanced Destruction of Plasmid-Loaded Microbubbles Improves Vasoreactivity , 2002, Circulation.

[9]  M. Wheatley,et al.  Contrast agents for diagnostic ultrasound: development and evaluation of polymer-coated microbubbles. , 1990, Biomaterials.

[10]  Alexander L. Klibanov,et al.  Microbubble Contrast Agents: Targeted Ultrasound Imaging and Ultrasound-Assisted Drug-Delivery Applications , 2006, Investigative radiology.

[11]  B. Goldberg,et al.  American Institute of Ultrasound in Medicine Recommendations for Contrast‐Enhanced Liver Ultrasound Imaging Clinical Trials , 2007, Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine.

[12]  Katherine W Ferrara,et al.  Therapeutic effects of paclitaxel-containing ultrasound contrast agents. , 2006, Ultrasound in medicine & biology.

[13]  R. Vandenbroucke,et al.  Ultrasound assisted siRNA delivery using PEG-siPlex loaded microbubbles. , 2008, Journal of Controlled Release.

[14]  Hairong Zheng,et al.  Acoustically-active microbubbles conjugated to liposomes: characterization of a proposed drug delivery vehicle. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[15]  Sanjiv Kaul,et al.  Targeted tissue transfection with ultrasound destruction of plasmid-bearing cationic microbubbles. , 2003, Ultrasound in medicine & biology.

[16]  Junru Wu,et al.  Ultrasound, cavitation bubbles and their interaction with cells. , 2008, Advanced drug delivery reviews.

[17]  R Gramiak,et al.  Echocardiography of the aortic root. , 1968, Investigative radiology.

[18]  P. Dayton,et al.  Experimental and theoretical evaluation of microbubble behavior: effect of transmitted phase and bubble size , 2000, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[19]  A. Klibanov,et al.  Targeted delivery of gas-filled microspheres, contrast agents for ultrasound imaging. , 1999, Advanced drug delivery reviews.

[20]  Eleanor Stride,et al.  Novel microbubble preparation technologies , 2008 .

[21]  M. Wheatley,et al.  Surfactant-stabilized microbubbles as ultrasound contrast agents : stability study of Span 60 and Tween 80 mixtures using a Langmuir trough , 1993 .

[22]  Paul A Dayton,et al.  Lateral phase separation in lipid-coated microbubbles. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[23]  Odd Helge Gilja,et al.  Ultrasound-directed drug delivery. , 2007, Current pharmaceutical biotechnology.

[24]  Jiri Sklenar,et al.  Microvascular rheology of Definity microbubbles after intra-arterial and intravenous administration. , 2002, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[25]  Vassilis Sboros,et al.  Response of contrast agents to ultrasound. , 2008, Advanced drug delivery reviews.

[26]  P. Dayton,et al.  Acoustic radiation force in vivo: a mechanism to assist targeting of microbubbles. , 1999, Ultrasound in medicine & biology.

[27]  P. Dayton,et al.  Optical and acoustical observations of the effects of ultrasound on contrast agents , 1999, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[28]  A. Klibanov,et al.  Detection of Individual Microbubbles of Ultrasound Contrast Agents: Imaging of Free-Floating and Targeted Bubbles , 2004, Investigative radiology.

[29]  Paul A Dayton,et al.  Ultrasound radiation force enables targeted deposition of model drug carriers loaded on microbubbles. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[30]  C. Visser,et al.  Low-intensity ultrasound-exposed microbubbles provoke local hyperpolarization of the cell membrane via activation of BK(Ca) channels. , 2008, Ultrasound in medicine & biology.

[31]  J. Hossack,et al.  Acoustic radiation force enhances targeted delivery of ultrasound contrast microbubbles: in vitro verification , 2005, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[32]  P. Dayton,et al.  Influence of lipid shell physicochemical properties on ultrasound-induced microbubble destruction , 2005, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[33]  K. Nightingale,et al.  A preliminary evaluation of the effects of primary and secondary radiation forces on acoustic contrast agents , 1997, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[34]  Michael Reinhardt,et al.  Evaluation of gas-filled microparticles and sonoporation as gene delivery system: feasibility study in rodent tumor models. , 2005, Radiology.

[35]  Paul A Dayton,et al.  Targeted imaging using ultrasound , 2002, Journal of magnetic resonance imaging : JMRI.

[36]  David Needham,et al.  Mechanical Properties and Microstructure of Polycrystalline Phospholipid Monolayer Shells: Novel Solid Microparticles , 2003 .

[37]  A. Bouakaz,et al.  Effect of ultrasound-activated microbubbles on the cell electrophysiological properties. , 2007, Ultrasound in medicine & biology.

[38]  K. Bohlin,et al.  Prediction of respiratory distress syndrome by the microbubble stability test on gastric aspirates in newborns of less than 32 weeks’gestation , 2003, Acta paediatrica.

[39]  M. S. Plesset,et al.  On the stability of gas bubbles in liquid-gas solutions , 1950 .

[40]  Naoki Ishiguro,et al.  A MULTICENTRE STUDY , 2010 .

[41]  H. Katus,et al.  Therapeutic Use of Ultrasound Targeted Microbubble Destruction: A Review of Non-Cardiac Applications , 2006, Ultraschall in der Medizin.

[42]  Nico de Jong,et al.  Vibrating microbubbles poking individual cells: drug transfer into cells via sonoporation. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[43]  Elazer R. Edelman,et al.  Adv. Drug Delivery Rev. , 1997 .

[44]  Stefaan C De Smedt,et al.  Ultrasound-responsive polymer-coated microbubbles that bind and protect DNA. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[45]  Dexi Liu,et al.  Cationic transfection lipids. , 2003, Current medicinal chemistry.

[46]  Georg Schmitz,et al.  Bubble dynamics involved in ultrasonic imaging , 2006, Expert review of molecular diagnostics.

[47]  R. Shohet,et al.  Targeting vascular endothelium with avidin microbubbles. , 2005, Ultrasound in medicine & biology.

[48]  Y Wu,et al.  Acoustically active lipospheres containing paclitaxel: a new therapeutic ultrasound contrast agent. , 1998, Investigative radiology.

[49]  C. Pichon,et al.  Polymer-based gene delivery: a current review on the uptake and intracellular trafficking of polyplexes. , 2008, Current gene therapy.

[50]  H. Klocker,et al.  Microbubble-enhanced ultrasound to deliver an antisense oligodeoxynucleotide targeting the human androgen receptor into prostate tumours , 2006, The Journal of Steroid Biochemistry and Molecular Biology.

[51]  P. Dayton,et al.  A method for radiation-force localized drug delivery using gas-filled lipospheres , 2004, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[52]  A. Klibanov,et al.  Ligand-carrying gas-filled microbubbles: ultrasound contrast agents for targeted molecular imaging. , 2005, Bioconjugate chemistry.

[53]  Leaf Huang,et al.  Nonviral vectors in the new millennium: delivery barriers in gene transfer. , 2001, Human gene therapy.

[54]  R. Gillies,et al.  DNA and polylysine adsorption and multilayer construction onto cationic lipid-coated microbubbles. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[55]  K. Tachibana,et al.  The Use of Ultrasound for Drug Delivery , 2001, Echocardiography.

[56]  A. Klibanov.  Ultrasound molecular imaging with targeted microbubble contrast agents , 2007, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[57]  Paul A Dayton,et al.  Molecular ultrasound imaging using microbubble contrast agents. , 2007, Frontiers in bioscience : a journal and virtual library.

[58]  Raffi Bekeredjian,et al.  Ultrasound-Targeted Microbubble Destruction Can Repeatedly Direct Highly Specific Plasmid Expression to the Heart , 2003, Circulation.

[59]  R. Shohet,et al.  DNA-loaded albumin microbubbles enhance ultrasound-mediated transfection in vitro. , 2002, Ultrasound in medicine & biology.

[60]  Katsuro Tachibana.  Emerging technologies in therapeutic ultrasound: Thermal ablation to gene delivery , 2011, Human Cell.

[61]  Paul A. Dayton,et al.  Optical observation of lipid- and polymer-shelled ultrasound microbubble contrast agents , 2004 .

[62]  K. Suslick,et al.  Air-filled proteinaceous microbubbles: synthesis of an echo-contrast agent. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[63]  R V Shohet,et al.  Echocardiographic destruction of albumin microbubbles directs gene delivery to the myocardium. , 2000, Circulation.

[64]  James J. Choi,et al.  Noninvasive, transcranial and localized opening of the blood-brain barrier using focused ultrasound in mice. , 2007, Ultrasound in medicine & biology.

[65]  H. Möhwald,et al.  Gas-filled polyelectrolyte capsules. , 2005, Angewandte Chemie.

[66]  Raffi Bekeredjian,et al.  Use of ultrasound contrast agents for gene or drug delivery in cardiovascular medicine. , 2005, Journal of the American College of Cardiology.

[67]  Raffi Bekeredjian,et al.  Augmentation of cardiac protein delivery using ultrasound targeted microbubble destruction. , 2005, Ultrasound in medicine & biology.

[68]  J. D’Arrigo.  Stable Gas-In-Liquid Emulsions: Production in Natural Waters and Artificial Media , 1986 .

[69]  P. Dayton,et al.  Threshold of fragmentation for ultrasonic contrast agents. , 2001, Journal of biomedical optics.

[70]  Muthupandian Ashokkumar,et al.  Ultrasonic synthesis of stable, functional lysozyme microbubbles. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[71]  H. Katus,et al.  Ultrasound targeted microbubble destruction for drug and gene delivery , 2008, Expert opinion on drug delivery.

[72]  R. Guy,et al.  Ultrasound-mediated gene delivery: influence of contrast agent on transfection. , 2007, Bioconjugate chemistry.

[73]  Flemming Forsberg,et al.  Ultrasound Contrast Agents: Basic Principles and Clinical Applications , 2001 .

[74]  Alexander L. Klibanov,et al.  Microbubbles in ultrasound-triggered drug and gene delivery. , 2008, Advanced drug delivery reviews.

[75]  C. Porter,et al.  Targeted retroviral gene delivery using ultrasound , 2007, The journal of gene medicine.

[76]  Paul A. Dayton,et al.  Optical observation of contrast agent destruction , 2000 .

[77]  Mark Borden,et al.  Ultrasound microbubble contrast agents: fundamentals and application to gene and drug delivery. , 2007, Annual review of biomedical engineering.

[78]  E. Unger,et al.  Therapeutic applications of lipid-coated microbubbles. , 2004, Advanced drug delivery reviews.

[79]  R. Eckersley,et al.  Acoustic characterization of contrast agents for medical ultrasound imaging , 2003 .

[80]  D. Scherman,et al.  A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[81]  P. Dayton,et al.  Mechanisms of contrast agent destruction , 2001, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[82]  T. Leighton.  The Acoustic Bubble , 1994 .

[83]  Jonathan R. Lindner,et al.  Microbubbles in medical imaging: current applications and future directions , 2004, Nature Reviews Drug Discovery.