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Optison™ Albumin Microspheres in Ultrasound-Assisted Gene Therapy and Drug Delivery

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Albumin in Medicine

Abstract

Optison™ (Perflutren Protein-Type A Microspheres Injectable Suspension, USP) is a sterile non-pyrogenic suspension of microspheres of human serum albumin with perflutren (also known as perfluoropropane). Optison™ microspheres are micrometre-sized gas-filled bubbles that have a shell consisting of human albumin. The size range is 2–4 μm in diameter and 95 % are less than 10 μm. This means that intravenously injected Optison™ may pass through the pulmonary capillary bed and access all parts of the systemic vasculature. The size distribution, shell properties and gas core provide a bubble that oscillates in response to and scatters ultrasound at frequencies useful for clinical imaging. The established use of Optison™ is in the field of echocardiography, where it provides echogenic contrast enhancement for suboptimal echocardiograms.

Optison™ is currently marketed in North America and Europe where researchers may gain access to the product for research and experimental use under their own institutional processes. One such experimental use that has shown promise is the use of ultrasound combined with a microbubble agent to induce transient changes to biological tissue with the aim of increasing delivery and penetration of therapeutic molecules. It has been known for decades that microbubbles can act as nucleation sites for a range of ultrasound-induced physical effects such as stable cavitation, inertial cavitation and jetting. These phenomena have been shown to have direct physical effects on biological membranes in the vicinity of the microbubble such as the creation of pores (sonoporation) which can persist for seconds up to several minutes depending on their size and the level of impact to the host cell. This approach has been applied as an alternative to viral vectors to address the significant challenge of delivering genetic material for anticancer and cardiovascular gene therapy. There are approximately 50 research papers on the use of Optison™ to enhance the transfection of oligonucleotides and plasmid DNA. This chapter will introduce Optison™ and its characteristics in the context of established use in diagnostic clinical imaging and experimental use in the delivery of therapeutic molecules. The methodology and results in the field of drug delivery and gene therapy will be reviewed and summarised in the context of effectiveness, potential for clinical translation and potential impact in medicine.

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Notes

  1. 1.

    Perfluoropropane is also known as perflutren and octafluoropropane, the chemical formula of which is C3F8.

  2. 2.

    Duty cycle, DC, is the percentage time that ultrasound transmission takes place during treatment. Therefore, DC of 100 % is continuous wave.

  3. 3.

    Mechanical index is a measure of ultrasound intensity. MI = peak negative pressure/square root of ultrasound centre frequency.

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Authors and Affiliations

  1. GE Healthcare, Life Sciences, The Grove Centre, White Lion Road, Amersham, Buckinghamshire, HP7 9LL, UK

    Alex Jackson, Adrian Smith & Christina K. Kalli

  2. General Electric Global Research, Niskayuna, NY, USA

    Jason W. Castle

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  1. Alex Jackson
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  2. Jason W. Castle
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  3. Adrian Smith
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  4. Christina K. Kalli
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Correspondence to Alex Jackson .

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Editors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan

    Masaki Otagiri

  2. School ofPharmacy,Fac of Health Sciences, Curtin University School ofPharmacy,Fac of Health Sciences, Perth, WA, Australia

    Victor Tuan Giam Chuang

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© 2016 Springer Science+Business Media Singapore

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Jackson, A., Castle, J.W., Smith, A., Kalli, C.K. (2016). Optison™ Albumin Microspheres in Ultrasound-Assisted Gene Therapy and Drug Delivery. In: Otagiri, M., Chuang, V. (eds) Albumin in Medicine. Springer, Singapore. https://doi.org/10.1007/978-981-10-2116-9_7

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