ICUS Weekly News Monitor 10-29-2015

1.  International Journal of Pharmaceutics,  Nov 30, 2015,  Acoustic Cluster Therapy (ACT) – A novel concept for ultrasound mediated, targeted drug delivery     Authors:  Per Sontuma, et al
2.  Echocardiography,  October 2015,  TIA Caused by Contrast Echocardiography in Patient with Platypnea–Orthodeoxia     Authors: Goran Loncar M.D. et al
International Journal of Pharmaceutics
Volume 495, Issue 2, Pages 1019–1027
Nov 30, 2015
Acoustic Cluster Therapy (ACT) – A novel concept for ultrasound mediated, targeted drug delivery
Authors:  Per Sontuma a, Svein Kvålea a, Andrew John Healeya a, Roald Skurtveitb b, Rira Watanabec c, Manabu Matsumurac c, Jonny Østensend d,
a Phoenix Solutions AS, PO Box 4741, N-0421 Oslo, Norway
b Institute for Energy Technology, Instituttveien 18, 2007 Kjeller, Norway
c Daiichi Sankyo Co., 3-5-1, Nihonbashi Honcho, Chuo-ku, Tokyo, 103-8426 Japan
d Inven2 AS, PO Box 1061 Blindern, N-0316 Oslo, Norway
A novel approach for ultrasound (US) mediated drug delivery – Acoustic Cluster Therapy (ACT) – is proposed, and basic characteristics of the ACT formulation are elucidated. The concept comprises administration of free flowing clusters of negatively charged microbubbles and positively charged microdroplets. The clusters are activated within the target pathology by diagnostic US, undergo an ensuing liquid-to-gas phase shift and transiently deposit 20–30 μm large bubbles in the microvasculature, occluding blood flow for ∼5–10 min. Further application of US will induce biomechanical effects that increases the vascular permeability, leading to a locally enhanced extravasation of components from the vascular compartment (e.g. released or co-administered drugs). Methodologies are detailed for determination of vital in-vitro characteristics of the ACT compound; cluster concentration and size distribution. It is shown how these attributes can be engineered through various formulation parameters, and their significance as predictors of biological behaviour, such as deposit characteristics, is demonstrated by US imaging in a dog model. Furthermore, in-vivo properties of the activated ACT bubbles are studied by intravital microscopy in a rat model, confirming the postulated behaviour of the concept.
DOI: 10.1111/echo.12970
Volume 32, Issue 10,  pages 1585–1587, October 2015
October 2015
TIA Caused by Contrast Echocardiography in Patient with Platypnea–Orthodeoxia
Authors: Goran Loncar M.D.1,2, Laurent Payot M.D.1,* and Mathieu Dubois M.D.3
1Institute of Cardiology, University Hospital Pitie Salpetriere, Paris, France
2Cardiology Department, Clinical Hospital Zvezdara, Belgrade, Serbia
3Department of Pneumology, University Hospital Pitie Salpetriere, Paris, France
Platypnea–orthodeoxia syndrome (POS) is a rare clinical disorder characterized by dyspnea caused by the upright position and relieved at recumbent position. Few cases of POS and stroke were reported in literature, and the association between stroke and POS with evidence of patent foramen ovale (PFO) is rare. Stroke may occur in patients with cardiac shunt who undergo contrast echocardiography. We present a patient with POS who experienced transitory ischemic attack (TIA) most likely caused by injection of agitated saline microbubbles during screen for PFO. No case report of TIA/stroke during contrast echocardiography in patients with POS has previously been published.

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