Polymer Microbubbles As Diagnostic and Therapeutic Gas Delivery Device

Abstract

Nitric oxide plays a central role in controlling arterial thrombosis and in cardiovascular diseases by inhibiting the platelet aggregation process. This process is regulated by giving a deactivating signal for the protein membrane integrins, the major platelet adhesion receptors. The localized production of NO, naturally occurring in arterial vessels, is carried out by the NO synthase enzymatic system. Inhibition of platelets aggregation in the coagulation cascade process is due to the antagonist action of NO toward integrin-fibrinogen induced platelet adhesion. However, sometimes the natural supply of NO is not sufficient to prevent clotting. The design of devices for suitable transport and delivery of NO is therefore important. We are developing a new concept of drug delivery in which NO release can be performed by means of polymer shelled microbubbles. The NO release can theoretically be concentrated in vessels with acute thrombosis by bursting of the microparticles upon insonification. This feature is linked to the structural and mechanical properties of the particles shell and it would make minimally invasive local theraphy of acute vascular disease feasible. In this paper, we present a study on some new structural and mechanical features of this microdevice supporting its NO loading capacity and in vitro efficacy in preventing the formation of a clot by releasing NO.

A new ultrasound-based approach to visualize target specific polymeric contrast agent

“…When the SA was applied, the detection of polymeric CA was improved compared to existing contrast algorithms. The poor performance of the existing contrast algorithms in visualizing the polymeric CA might be due to the large shell thickness of the polymeric CA in comparison with commercially available CA [9]. The thick shell will increase the shear viscosity and the shear modulus of the encapsulated bubble, which in turn results in increased damping of the bubble oscillation and hence a less well-defined resonance frequency.…”

In Situ Synchrotron Radiation X‐Ray Microspectroscopy of Polymer Microcontainers

“…[41][42][43][44] Stable air-filled MBs were prepared by cross-linking telechelic PVA (i.e., PVA bearing aldehydes at the chain ends) at the water/air interface. The aliphatic groups of the PVA chains at the airpolymer shell-water boundary are arranged at the air phase while the hydroxyl groups point toward the aqueous phase (see the sketch in Figure 5).…”

Core–shell silica@chitosan nanoparticles and hollow chitosan nanospheres using silica nanoparticles as templates: Preparation and ultrasound bubble application

“…The transfection efficiency of the non-viral systems is not comparable to the efficiency of the viral delivers (Kodama, Katayama, Shoji, & Nakashima, 2006;Strand et al, 2005). Therefore, the relatively high transfection efficiency of the gas-filled microbubbles is noteworthy (Cavalier et al, 2008;Cheng, Xia, & Chan, 2004;Lentacker et al, 2006;Marmottant & Hilgenfeldt, 2003;Mehier-Humbert, Bettinger, Yan, & Gyu (2005); Mehier-Humbert et al, 2007;Suzuki et al, 2007;Taniyama et al, 2002). The gas-filled microbubbles are ultrasound contrast particles for molecular imaging (Klibanov, 2005), which can be utilized in gene delivery through the ultrasound-induced cavitation technique.…”

“…The gas-filled microbubbles are ultrasound contrast particles for molecular imaging (Klibanov, 2005), which can be utilized in gene delivery through the ultrasound-induced cavitation technique. The gas-filled bubbles should have sizes smaller than red blood cells for intravascular applications (Cavalier et al, 2008;Suzuki et al, 2007), and are easily decorated with other materials.…”