Opening doors with ultrasound and microbubbles: Beating biological barriers to promote drug delivery.

Apart from its clinical use in imaging, ultrasound has been thoroughly investigated as a tool to enhance drug delivery in a wide variety of applications. Therapeutic ultrasound, as such or combined with cavitating nuclei or microbubbles, has been explored to cross or permeabilize different biological barriers. This ability to access otherwise impermeable tissues in the body makes the combination of ultrasound and therapeutics very appealing to enhance drug delivery in situ. This review gives an overview of the most important biological barriers that can be tackled using ultrasound and aims to provide insight on how ultrasound has shown to improve accessibility as well as the biggest hurdles. In addition, we discuss the clinical applicability of therapeutic ultrasound with respect to the main challenges that must be addressed to enable the further progression of therapeutic ultrasound towards an effective, safe and easy-to-use treatment tailored for drug delivery in patients.

Sonoprinting liposomes on tumor spheroids by microbubbles and ultrasound.

Ultrasound-triggered drug-loaded microbubbles have great potential for drug delivery due to their ability to locally release drugs and simultaneously enhance their delivery into the target tissue. We have recently shown that upon applying ultrasound, nanoparticle-loaded microbubbles can deposit nanoparticles onto cells grown in 2D monolayers, through a process that we termed "sonoprinting". However, the rigid surfaces on which cell monolayers are typically growing might be a source of acoustic reflections and aspherical microbubble oscillations, which can influence microbubble-cell interactions. In the present study, we aim to reveal whether sonoprinting can also occur in more complex and physiologically relevant tissues, by using free-floating 3D tumor spheroids as a tissue model. We show that both monospheroids (consisting of tumor cells alone) and cospheroids (consisting of tumor cells and fibroblasts, which produce an extracellular matrix) can be sonoprinted. Using doxorubicin-liposome-loaded microbubbles, we show that sonoprinting allows to deposit large amounts of doxorubicin-containing liposomes to the outer cell layers of the spheroids, followed by doxorubicin release into the deeper layers of the spheroids, resulting in a significant reduction in cell viability. Sonoprinting may become an attractive approach to deposit drug patches at the surface of tissues, thereby promoting the delivery of drugs into target tissues.

Layered acoustofluidic resonators for the simultaneous optical and acoustic characterisation of cavitation dynamics, microstreaming, and biological effects.

The study of the effects of ultrasound-induced acoustic cavitation on biological structures is an active field in biomedical research. Of particular interest for therapeutic applications is the ability of oscillating microbubbles to promote both cellular and tissue membrane permeabilisation and to improve the distribution of therapeutic agents in tissue through extravasation and convective transport. The mechanisms that underpin the interaction between cavitating agents and tissues are, however, still poorly understood. One challenge is the practical difficulty involved in performing optical microscopy and acoustic emissions monitoring simultaneously in a biologically compatible environment. Here we present and characterise a microfluidic layered acoustic resonator (µLAR) developed for simultaneous ultrasound exposure, acoustic emissions monitoring, and microscopy of biological samples. The µLAR facilitates in vitro ultrasound experiments in which measurements of microbubble dynamics, microstreaming velocity fields, acoustic emissions, and cell-microbubble interactions can be performed simultaneously. The device and analyses presented provide a means of performing mechanistic in vitro studies that may benefit the design of predictable and effective cavitation-based ultrasound treatments.

Emergence of dengue virus serotype 3 on Mayotte Island, Indian Ocean.

A serosurvey carried out in 2006 in Mayotte, a French overseas collectivity in the Indian Ocean, confirmed previous circulation of dengue virus (DENV) on the island, but since the set up of a laboratory-based surveillance of dengue-like illness in 2007, no case of DENV has been confirmed. In response to an outbreak of DENV-3 on Comoros Islands in March 2010 surveillance of dengue-like illness in Mayotte was enhanced. By September 15, 76 confirmed and 31 probable cases of DENV have been identified in Mayotte. In urban and periurban settings on the island, Aedes albopictus is the predominant Aedes species, but Ae. aegyptii remains the most common species in rural areas. Given the epidemic potential of dengue virus in Mayotte, adequate monitoring including early detection of cases, timely investigation and sustained mosquito control actions remain essential.

Epidemiology, surveillance and control of infectious diseases in the European overseas countries and territories, 2011.

The 25 European overseas countries and territories (OCTs) are closely associated with the European Union (EU) through the four related UE Member States: Denmark, France, the Netherlands and the United Kingdom. In 2008 and 2009, these four EU Member States, in association with the European Centre for Disease Prevention and Control (ECDC), reviewed the OCTs' needs, with the objectives of documenting their capacity to prevent and respond to infectious diseases outbreaks, and identifying deficiencies. This Euroroundup is based on the review's main findings, and presents an overview of the OCTs' geography and epidemiology, briefly introduces the legal basis on which they are linked to the EU and describes the surveillance and infectious disease response systems. As a result of their diversity the OCTs have heterogeneous epidemiological profiles. A common factor, however, is that the main burden of disease is non-communicable. Nevertheless, OCTs remain vulnerable to infectious diseases outbreaks. Their capacity for surveillance, early detection and response to such outbreaks is generally limited, with laboratory capacity issues and lack of human resources. Avenues for capacity strengthening should be explored by the OCTs and the related EU Member States, in collaboration with ECDC and regional public health networks where these exist.

[Influenza A (H1N1) 2009 surveillance on Mayotte island: the challenge of setting up a new system facing the pandemic]. / La grippe A (H1N1) 2009 à Mayotte: mise en place d'une surveillance épidémiologique face à la menace de pandémie.

In response to the threat of the pandemic influenza A (H1N1) 2009 virus in Mayotte Island, influenza surveillance needed to be set up in a matter of weeks, to detect the introduction of the pandemic virus and monitor its spread and impact on public health. Surveillance was based on different systems, including a sentinel practitioner network for influenza-like illness, surveillance of the activity at the hospital emergency departments, virological surveillance, surveillance of severe and fatal cases, and data collection on sale of antipyretic and anti-viral drugs. Despite some weaknesses of the surveillance, results showed a good correlation between all systems, describing an epidemic period of approximately 8-9 weeks, with a peak between weeks 37 and 40, followed by a rapid decrease. Besides allowing monitoring and describing the impact of pandemic H1N1 2009 virus in Mayotte, the surveillance system provided an opportunity to create networks and globally strengthened surveillance of infectious diseases in the Island.