Polymer microbubbles as diagnostic and therapeutic gas delivery device

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.