Novel microbubble preparation technologies

Gas microbubbles, stabilised by a surfactant or polymer coating, have become well established over the past 20–30 years as the most effective type of contrast agent available for ultrasound radiography. More recently, their potential for use in therapeutic applications including targeted drug delivery, gene therapy, thrombolysis and focused ultrasound surgery has also been investigated. Developments in both diagnostic and therapeutic applications have greatly increased the need for more advanced preparation technologies which provide a high degree of control over microbubble size, composition, stability and uniformity. Conventional processing techniques such as sonication and high shear emulsification offer high yield and low cost production but poor control over microbubble size and uniformity. This is being addressed by the development of new technologies, such as membrane emulsification, inkjet printing, electrohydrodynamic atomisation and microfluidic processing which offer significant improvements in terms of control over microbubble characteristics. The aim of this paper is to review the range of techniques available for microbubble preparation and how these have evolved to keep pace with advances in clinical practice.

[1]  E Stride,et al.  Preparation of suspensions of phospholipid-coated microbubbles by coaxial electrohydrodynamic atomization , 2009, Journal of The Royal Society Interface.

[2]  M. Edirisinghe,et al.  Generation of multilayered structures for biomedical applications using a novel tri-needle coaxial device and electrohydrodynamic flow , 2008, Journal of The Royal Society Interface.

[3]  E Stride,et al.  Increasing the nonlinear character of microbubble oscillations at low acoustic pressures , 2008, Journal of The Royal Society Interface.

[4]  E Stride,et al.  The influence of surface adsorption on microbubble dynamics , 2008, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[5]  E. Stride,et al.  Novel methods for preparing phospholipid coated microbubbles , 2008, European Biophysics Journal.

[6]  Eleanor Stride,et al.  Dynamics of bubble formation in highly viscous liquids. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[7]  Paul A Dayton,et al.  Maintaining monodispersity in a microbubble population formed by flow-focusing. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[8]  M. Edirisinghe,et al.  Novel co-axial electrohydrodynamic in-situ preparation of liquid-filled polymer-shell microspheres for biomedical applications , 2008, Journal of microencapsulation.

[9]  M. Edirisinghe,et al.  Generation of microbubbles for diagnostic and therapeutic applications using a novel device , 2008, Journal of drug targeting.

[10]  A. Bouakaz,et al.  Radial Modulation of Microbubbles for Ultrasound Contrast Imaging , 2007, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[11]  Philippe Marmottant,et al.  Role of the channel geometry on the bubble pinch-off in flow-focusing devices. , 2007, Physical review letters.

[12]  J. Bull.  The application of microbubbles for targeted drug delivery , 2007, Expert opinion on drug delivery.

[13]  E Stride,et al.  Preparation of microbubble suspensions by co-axial electrohydrodynamic atomization. , 2007, Medical engineering & physics.

[14]  S A Wickline,et al.  Fibrin-targeted perfluorocarbon nanoparticles for targeted thrombolysis. , 2007, Nanomedicine.

[15]  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.

[16]  Zhong-gao Gao,et al.  Multifunctional nanoparticles for combining ultrasonic tumor imaging and targeted chemotherapy. , 2007, Journal of the National Cancer Institute.

[17]  Eleanor Stride,et al.  Microbubbling by co-axial electrohydrodynamic atomization , 2007, Medical & Biological Engineering & Computing.

[18]  Ronald A. Roy,et al.  Cavitational mechanisms in ultrasound-accelerated fibrinolysis. , 2007, Ultrasound in medicine & biology.

[19]  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.

[20]  Paul A Dayton,et al.  On-chip generation of microbubbles as a practical technology for manufacturing contrast agents for ultrasonic imaging. , 2007, Lab on a chip.

[21]  M. Goto,et al.  Spontaneous formation behavior of uniform-sized microbubbles from Shirasu porous glass (SPG) membranes in the absence of water-phase flow , 2007 .

[22]  Hua'an Zhang,et al.  Preparation of Monodispersed Polymer Microspheres by SPG Membrane Emulsification‐Solvent Evaporation Technology , 2007 .

[23]  T. Okinaga,et al.  Local delivery system of cytotoxic agents to tumors by focused sonoporation , 2007, Cancer Gene Therapy.

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

[25]  David Cosgrove,et al.  Ultrasound contrast agents: an overview. , 2006, European journal of radiology.

[26]  J. Pikkemaat,et al.  Preparation of monodisperse polymer particles and capsules by ink-jet printing , 2006 .

[27]  M. Goto,et al.  Size control of nanobubbles generated from Shirasu-porous-glass (SPG) membranes , 2006 .

[28]  M. Edirisinghe,et al.  A novel method for the preparation of biodegradable microspheres for protein drug delivery , 2006, Journal of The Royal Society Interface.

[29]  Wolfgang Schmidt,et al.  Novel manufacturing process of hollow polymer microspheres , 2006 .

[30]  G. Whitesides.  The origins and the future of microfluidics , 2006, Nature.

[31]  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.

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

[33]  Raquel Delgado-Mederos,et al.  Microbubble administration accelerates clot lysis during continuous 2-MHz ultrasound monitoring in stroke patients treated with intravenous tissue plasminogen activator. , 2006, Stroke.

[34]  Changyou Gao,et al.  Polylactide hollow spheres fabricated by interfacial polymerization in an oil-in-water emulsion system , 2006 .

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

[36]  Hai-Dong Liang,et al.  Preparation, characterization and in vivo observation of phospholipid-based gas-filled microbubbles containing hirudin. , 2005, Ultrasound in medicine & biology.

[37]  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.

[38]  R. Guy,et al.  Ultrasound-mediated gene delivery: kinetics of plasmid internalization and gene expression. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[39]  Xiao Zhou,et al.  Preparation and evaluation of poly(L-lactide-co-glycolide) (PLGA) microbubbles as a contrast agent for myocardial contrast echocardiography. , 2005, Journal of biomedical materials research. Part B, Applied biomaterials.

[40]  Mitsutoshi Nakajima,et al.  The generation of highly monodisperse droplets through the breakup of hydrodynamically focused microthread in a microfluidic device , 2004 .

[41]  George M. Whitesides,et al.  Formation of monodisperse bubbles in a microfluidic flow-focusing device , 2004 .

[42]  Gregory T. Clement,et al.  Perspectives in clinical uses of high-intensity focused ultrasound. , 2004, Ultrasonics.

[43]  Mohan Edirisinghe,et al.  Electrostatic atomisation of a ceramic suspension , 2004 .

[44]  David A. Weitz,et al.  A new device for the generation of microbubbles , 2004 .

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

[46]  D. McPherson,et al.  Novel Echogenic Drug-Immunoliposomes for Drug Delivery , 2004, Investigative radiology.

[47]  J. Bai,et al.  A microbubble agent improves the therapeutic efficiency of high intensity focused ultrasound: a rabbit kidney study , 2004, Urological Research.

[48]  J. Riess.  Fluorocarbon-based injectable gaseous microbubbles for diagnosis and therapy , 2003 .

[49]  E Stride,et al.  Microbubble ultrasound contrast agents: A review , 2003, Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine.

[50]  P. Marmottant,et al.  Controlled vesicle deformation and lysis by single oscillating bubbles , 2003, Nature.

[51]  C. Holland,et al.  In vitro characterization of liposomes and Optison by acoustic scattering at 3.5 MHz. , 2003, Ultrasound in medicine & biology.

[52]  Eleanor Stride,et al.  On the destruction of microbubble ultrasound contrast agents. , 2003, Ultrasound in medicine & biology.

[53]  V. Awasthi,et al.  Circulation and biodistribution profiles of long-circulating PEG-liposomes of various sizes in rabbits. , 2003, International journal of pharmaceutics.

[54]  H. Stone,et al.  Formation of dispersions using “flow focusing” in microchannels , 2003 .

[55]  D. McPherson,et al.  A Physiologic Flow Chamber Model to Define Intravascular Ultrasound Enhancement of Fibrin Using Echogenic Liposomes , 2002, Investigative radiology.

[56]  S. Rajagopalan,et al.  Ultrasound-mediated transfection of canine myocardium by intravenous administration of cationic microbubble-linked plasmid DNA. , 2002, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[57]  D. Cosgrove,et al.  Advances in ultrasound. , 2002, Clinical radiology.

[58]  G. Bartsch,et al.  Detection of prostate cancer with a microbubble ultrasound contrast agent , 2001, The Lancet.

[59]  D. Cosgrove,et al.  Microbubble contrast agents: a new era in ultrasound , 2001, BMJ : British Medical Journal.

[60]  Mitsutoshi Nakajima,et al.  The effect of the hydrophobicity of microchannels and components in water and oil phases on droplet formation in microchannel water-in-oil emulsification , 2001 .

[61]  W L Nyborg,et al.  Biological effects of ultrasound: development of safety guidelines. Part II: general review. , 2001, Ultrasound in medicine & biology.

[62]  Douglas L. Miller,et al.  Sonoporation of monolayer cells by diagnostic ultrasound activation of contrast-agent gas bodies. , 2000, Ultrasound in medicine & biology.

[63]  G. Trägårdh,et al.  Membrane emulsification — a literature review , 2000 .

[64]  S. Kaul,et al.  Microbubble persistence in the microcirculation during ischemia/reperfusion and inflammation is caused by integrin- and complement-mediated adherence to activated leukocytes. , 2000, Circulation.

[65]  K. Bjerknes,et al.  Preparation of Polymeric Microcapsules: Formulation Studies , 2000, Drug development and industrial pharmacy.

[66]  D O Cosgrove,et al.  Stimulated acoustic emission to image a late liver and spleen-specific phase of Levovist in normal volunteers and patients with and without liver disease. , 1999, Ultrasound in medicine & biology.

[67]  K. Ohmori,et al.  Enhancement of ultrasound-accelerated thrombolysis by echo contrast agents: dependence on microbubble structure. , 1999, Ultrasound in medicine & biology.

[68]  K. Suslick,et al.  Acoustic cavitation and its chemical consequences , 1999, Philosophical Transactions of the Royal Society of London. Series A: Mathematical, Physical and Engineering Sciences.

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

[70]  E. Unger,et al.  MRX 501: a novel ultrasound contrast agent with therapeutic properties. , 1998, Academic radiology.

[71]  A R Jayaweera,et al.  Quantification of myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a constant venous infusion. , 1998, Circulation.

[72]  N de Jong,et al.  Effect of ultrasound on the release of micro-encapsulated drugs. , 1998, Ultrasonics.

[73]  K. Bjerknes,et al.  Preparation of polymeric microbubbles: formulation studies and product characterisation , 1997 .

[74]  Wamadeva Balachandran,et al.  Towards particle-by-particle deposition of ceramics using electrostatic atomization , 1997 .

[75]  M. Wheatley,et al.  Langmuir Trough Study of Surfactant Mixtures Used in the Production of a New Ultrasound Contrast Agent Consisting of Stabilized Microbubbles , 1996 .

[76]  J. Kuszak,et al.  Development of inherently echogenic liposomes as an ultrasonic contrast agent. , 1996, Journal of pharmaceutical sciences.

[77]  K. Tachibana,et al.  Albumin microbubble echo-contrast material as an enhancer for ultrasound accelerated thrombolysis. , 1995, Circulation.

[78]  T. Skotland,et al.  Physical and biochemical characterization of Albunex, a new ultrasound contrast agent consisting of air‐filled albumin microspheres suspended in a solution of human albumin , 1994, Biotechnology and applied biochemistry.

[79]  M. Arditi,et al.  Polymeric microballoons as ultrasound contrast agents. Physical and ultrasonic properties compared with sonicated albumin. , 1992, Investigative radiology.

[80]  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.

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

[82]  E. Carstensen,et al.  Ultrasonic detection of cavitation at catheter tips. , 1970, The American journal of roentgenology, radium therapy, and nuclear medicine.

[83]  H. Feigenbaum,et al.  Identification of Ultrasound Echoes from the Left Ventricle by Use of Intracardiac Injections of Indocyanine Green , 1970, Circulation.

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

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

[86]  J. G. Miller,et al.  Targeting of ultrasound contrast material. An in vitro feasibility study. , 1997, Acta radiologica. Supplementum.

[87]  Douglas L. Miller,et al.  Transfection of a reporter plasmid into cultured cells by sonoporation in vitro. , 1997, Ultrasound in medicine & biology.

[88]  Kenneth S. Suslick,et al.  Protein microencapsulation of nonaqueous liquids , 1990 .

[89]  F J Ten Cate,et al.  Two-dimensional contrast echocardiography. I. In vitro development and quantitative analysis of echo contrast agents. , 1984, Journal of the American College of Cardiology.