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

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.

Silicon-containing nanocarriers for targeted drug delivery: synthesis, physicochemical properties and acute toxicity

“…More research is needed to study the biodegradation and biodistribution of this new hybrid NP. Previously, we have shown that non-modified SiO 2 NPs can accumulate within the anatomical area at risk after regional myocardial ischemia-reperfusion (Galagudza et al, 2012). In combination with the results of the present study, these data provide a solid basis for further investigation of siliconcontaining NPs as drug carriers.…”

“…Recent work has shown that immobilization of adenosine on the surface of SiO 2 NPs resulted in the enhancement of adenosine-mediated infarct size limitation (Galagudza et al, 2012). In addition, immobilization of adenosine on the surface of SiO 2 NPs attenuated the hypotensive effect of adenosine.…”

“…While passive-and active-targeted drug delivery have been intensively investigated in cancer models, the possibility of delivering cardioprotective drugs to the area of myocardial ischemia-reperfusion is much less studied (Galagudza et al, 2012;Levchenko et al, 2012;Li et al, 2015). To date, few studies that show a reduction in irreversible myocardial ischemia-reperfusion injury after the administration of liposome-embedded adenosine (Takahama et al, 2009), or adenosine adsorbed on the surface of the silica NPs (SiO 2 NPs) (Galagudza et al, 2012) have been reported.…”

“…To date, few studies that show a reduction in irreversible myocardial ischemia-reperfusion injury after the administration of liposome-embedded adenosine (Takahama et al, 2009), or adenosine adsorbed on the surface of the silica NPs (SiO 2 NPs) (Galagudza et al, 2012) have been reported. We have previously shown that SiO 2 NPs are non-toxic during acute intravenous administration (Galagudza et al, 2010a,b).…”

Tissue distribution and excretion kinetics of orally administered silica nanoparticles in rats

“…It was reported that silica nanoparticles undergo gradual biodegradation both in vitro and in vivo, resulting in the formation of silicic acid (ortho-, meta-, di-, and trisilicates) by hydrolysis. 33,34 Predominant excretion forms of silica nanoparticles in urine are known to be silicic acid or oligomeric silica species. 35,36 Thus, sodium or potassium silicic acid salts could be excreted from the organs with the urine.…”