Ultrasound-mediated targeted drug delivery: recent success and remaining challenges.

The potential clinical value of developing a novel, nonviral, ultrasound-directed gene and drug delivery system is immense. Investigators soon will initiate clinical trials with the goal of treating a wide variety of maladies using noninvasive, ultrasound-based technology. The ongoing, scientific validation associated with promising preclinical success portents a novel range of therapeutics. The clinical utility and eventual clinical successes await vigorous testing. This review highlights the recent successes and challenges within the field of ultrasound-mediated drug delivery.

[1]  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.

[2]  M. Machluf,et al.  Efficient transfection of tumors facilitated by long-term therapeutic ultrasound in combination with contrast agent: from in vitro to in vivo setting , 2007, Cancer Gene Therapy.

[3]  G. Pelled,et al.  Ultrasound-based nonviral gene delivery induces bone formation in vivo , 2008, Gene Therapy.

[4]  Harald Becher,et al.  American Society of Echocardiography Consensus Statement on the Clinical Applications of Ultrasonic Contrast Agents in Echocardiography. , 2008, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[5]  G. Trinchieri,et al.  Innate resistance and inflammation. , 2009, Current opinion in immunology.

[6]  Raffi Bekeredjian,et al.  Efficient gene delivery to pancreatic islets with ultrasonic microbubble destruction technology. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

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

[8]  Win-Li Lin,et al.  Enhancement of focused ultrasound with microbubbles on the treatments of anticancer nanodrug in mouse tumors. , 2012, Nanomedicine : nanotechnology, biology, and medicine.

[9]  Harald Becher,et al.  Contrast echocardiography: evidence-based recommendations by European Association of Echocardiography. , 2008, European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology.

[10]  S. D. De Smedt,et al.  Crucial factors and emerging concepts in ultrasound-triggered drug delivery. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[11]  T. Skotland,et al.  Biochemical characterization of air‐filled albumin microspheres , 1993, Biotechnology and applied biochemistry.

[12]  T. Skotland,et al.  Structure and organization of albumin molecules forming the shell of air‐filled microspheres: evidence for a monolayer of albumin molecules of multiple orientations stabilizing the enclosed air , 1996, Biotechnology and applied biochemistry.

[13]  Cheri X Deng,et al.  A review of physical phenomena associated with ultrasonic contrast agents and illustrative clinical applications. , 2002, Ultrasound in medicine & biology.

[14]  Conrad Coester,et al.  Microbubbles as ultrasound triggered drug carriers. , 2009, Journal of pharmaceutical sciences.

[15]  Raffi Bekeredjian,et al.  Optimization of ultrasound parameters for cardiac gene delivery of adenoviral or plasmid deoxyribonucleic acid by ultrasound-targeted microbubble destruction. , 2003, Journal of the American College of Cardiology.

[16]  K. Hoyt,et al.  Microbubble-mediated ultrasonic techniques for improved chemotherapeutic delivery in cancer , 2012, Journal of drug targeting.

[17]  R. Eckersley,et al.  Microbubble stability is a major determinant of the efficiency of ultrasound and microbubble mediated in vivo gene transfer. , 2009, Ultrasound in medicine & biology.

[18]  V. Ferrera,et al.  Feasibility of noninvasive cavitation-guided blood-brain barrier opening using focused ultrasound and microbubbles in nonhuman primates. , 2011, Applied physics letters.

[19]  Yao-Sheng Tung,et al.  Multi-modality safety assessment of blood-brain barrier opening using focused ultrasound and definity microbubbles: a short-term study. , 2010, Ultrasound in medicine & biology.

[20]  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.

[21]  Mark Borden,et al.  Microbubble Compositions, Properties and Biomedical Applications. , 2009, Bubble science engineering and technology.

[22]  Yang Du,et al.  Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1 , 2006, Nature Medicine.

[23]  Kullervo Hynynen,et al.  Effect of focused ultrasound applied with an ultrasound contrast agent on the tight junctional integrity of the brain microvascular endothelium. , 2008, Ultrasound in medicine & biology.

[24]  J. Nalbantoglu,et al.  Ultrasound increases plasmid-mediated gene transfer to dystrophic muscles without collateral damage. , 2002, Molecular therapy : the journal of the American Society of Gene Therapy.

[25]  S. Fazel,et al.  Ultrasound-targeted gene delivery induces angiogenesis after a myocardial infarction in mice. , 2009, JACC. Cardiovascular imaging.

[26]  K. Hynynen,et al.  Cellular mechanisms of the blood-brain barrier opening induced by ultrasound in presence of microbubbles. , 2004, Ultrasound in medicine & biology.

[27]  C. Porter,et al.  Spatial and acoustic pressure dependence of microbubble‐mediated gene delivery targeted using focused ultrasound , 2006, The journal of gene medicine.

[28]  T. Matsunaga,et al.  Diagnostic Ultrasound Combined With Glycoprotein IIb/IIIa–Targeted Microbubbles Improves Microvascular Recovery After Acute Coronary Thrombotic Occlusions , 2009, Circulation.

[29]  M. Hennerici,et al.  Clearance of albumin following ultrasound-induced blood–brain barrier opening is mediated by glial but not neuronal cells , 2011, Brain Research.

[30]  G. Hannon,et al.  A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4 , 1993, Nature.

[31]  J. Riess,et al.  Injectable microbubbles as contrast agents for diagnostic ultrasound imaging: the key role of perfluorochemicals. , 2003, Angewandte Chemie.

[32]  C. Visser,et al.  Transient permeabilization of cell membranes by ultrasound-exposed microbubbles is related to formation of hydrogen peroxide. , 2006, American journal of physiology. Heart and circulatory physiology.

[33]  H. Atkinson,et al.  Delivering the goods: viral and non-viral gene therapy systems and the inherent limits on cargo DNA and internal sequences , 2010, Genetica.

[34]  A. van Rossum,et al.  Ultrasound enhanced prehospital thrombolysis using microbubbles infusion in patients with acute ST elevation myocardial infarction: pilot of the Sonolysis study. , 2012, Ultrasound in medicine & biology.

[35]  S. Rosenberg,et al.  Adoptive cell therapy for the treatment of patients with metastatic melanoma. , 2009, Current opinion in immunology.

[36]  S. Kitamura,et al.  Nonviral delivery of siRNA into mesenchymal stem cells by a combination of ultrasound and microbubbles. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[37]  T. Skotland,et al.  Changes of protein solutions during storage: a study of albumin pharmaceutical preparations , 2010, Biotechnology and applied biochemistry.

[38]  P. Grayburn,et al.  Regeneration of Pancreatic Islets in Vivo by Ultrasound-Targeted Gene Therapy , 2010, Gene Therapy.

[39]  R. Vandenbroucke,et al.  Ultrasound assisted siRNA delivery using PEG-siPlex loaded microbubbles. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[40]  Kathleen A. Marshall,et al.  AAV2 Gene Therapy Readministration in Three Adults with Congenital Blindness , 2012, Science Translational Medicine.

[41]  R. Henning,et al.  Optimization of ultrasound and microbubbles targeted gene delivery to cultured primary endothelial cells , 2007, Journal of drug targeting.

[42]  M. Fishbein,et al.  Noninvasive in vivo clot dissolution without a thrombolytic drug: recanalization of thrombosed iliofemoral arteries by transcutaneous ultrasound combined with intravenous infusion of microbubbles. , 1998, Circulation.

[43]  S. Smedt,et al.  Lipoplex‐Loaded Microbubbles for Gene Delivery: A Trojan Horse Controlled by Ultrasound , 2007 .

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

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

[46]  P. Sontum,et al.  Physicochemical characteristics of Sonazoid, a new contrast agent for ultrasound imaging. , 2008, Ultrasound in medicine & biology.

[47]  Chih-Kuang Yeh,et al.  Concurrent blood-brain barrier opening and local drug delivery using drug-carrying microbubbles and focused ultrasound for brain glioma treatment. , 2012, Biomaterials.

[48]  P. Roberson,et al.  Intracranial Clot Lysis With Intravenous Microbubbles and Transcranial Ultrasound in Swine , 2004, Stroke.

[49]  Sheila Podell,et al.  Physical and biochemical stability of Optison®, an injectable ultrasound contrast agent , 1999, Biotechnology and applied biochemistry.

[50]  D. Adam,et al.  The effects of albumin-coated microbubbles in DNA delivery mediated by therapeutic ultrasound. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[51]  Zhigang Wang,et al.  Ultrasound-mediated microbubble destruction enhances VEGF gene delivery to the infarcted myocardium in rats. , 2004, Clinical imaging.

[52]  P. Grayburn,et al.  Transient overexpression of cyclin D2/CDK4/GLP1 genes induces proliferation and differentiation of adult pancreatic progenitors and mediates islet regeneration , 2012, Cell cycle.

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

[54]  Muthupandian Ashokkumar,et al.  The design of multifunctional microbubbles for ultrasound image-guided cancer therapy. , 2010, Current topics in medicinal chemistry.

[55]  Mustafa Kurt,et al.  Impact of contrast echocardiography on evaluation of ventricular function and clinical management in a large prospective cohort. , 2009, Journal of the American College of Cardiology.

[56]  C. Holland,et al.  Thrombolytic efficacy of tissue plasminogen activator-loaded echogenic liposomes in a rabbit thrombus model. , 2012, Thrombosis research.

[57]  J G Miller,et al.  Contrast Echocardiography: Current and Future Applications , 2000 .

[58]  E. Rosenthal,et al.  Microbubble Therapy Enhances Anti-tumor Properties of Cisplatin and Cetuximab In Vitro and In Vivo , 2012, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[59]  Nico de Jong,et al.  Ultrasound and Microbubble-Targeted Delivery of Macromolecules Is Regulated by Induction of Endocytosis and Pore Formation , 2009, Circulation research.

[60]  Kazuo Maruyama,et al.  Effective gene delivery with novel liposomal bubbles and ultrasonic destruction technology. , 2008, International journal of pharmaceutics.

[61]  Natalia Vykhodtseva,et al.  Targeted delivery of doxorubicin to the rat brain at therapeutic levels using MRI‐guided focused ultrasound , 2007, International journal of cancer.

[62]  S. Feinstein,et al.  The powerful microbubble: from bench to bedside, from intravascular indicator to therapeutic delivery system, and beyond. , 2004, American journal of physiology. Heart and circulatory physiology.

[63]  A. Brayman,et al.  Explorations of high-intensity therapeutic ultrasound and microbubble-mediated gene delivery in mouse liver , 2011, Gene Therapy.

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