Passive targeting of ischemic-reperfused myocardium with adenosine-loaded silica nanoparticles

Michael Galagudza¹, Dmitry Korolev¹, Viktor Postnov², Elena Naumisheva², Yulia Grigorova³, Ivan Uskov¹, Eugene Shlyakhto^1
1Institute of Experimental Medicine, VA Almazov Federal Heart, Blood and Endocrinology Center, ²Chemical Faculty, St Petersburg State University, ³Department of Pathophysiology, IP Pavlov State Medical University, St Petersburg, Russian Federation

Abstract: Pharmacological agents suggested for infarct size limitation have serious side effects when used at cardioprotective doses which hinders their translation into clinical practice. The solution to the problem might be direct delivery of cardioprotective drugs into ischemic-reperfused myocardium. In this study, we explored the potential of silica nanoparticles for passive delivery of adenosine, a prototype cardioprotective agent, into ischemic-reperfused heart tissue. In addition, the biodegradation of silica nanoparticles was studied both in vitro and in vivo. Immobilization of adenosine on the surface of silica nanoparticles resulted in enhancement of adenosine-mediated infarct size limitation in the rat model. Furthermore, the hypotensive effect of adenosine was attenuated after its adsorption on silica nanoparticles. We conclude that silica nanoparticles are biocompatible materials that might potentially be used as carriers for heart-targeted drug delivery.

Keywords: silica nanoparticles, targeted drug delivery, myocardium, ischemia, reperfusion