Targeted drug delivery into reversibly injured myocardium with silica nanoparticles: surface functionalization,  natural biodistribution, and acute toxicity

Abstract

Abstract:The clinical outcome of patients with ischemic heart disease can be significantly improved with the implementation of targeted drug delivery into the ischemic myocardium. In this paper, we present our original findings relevant to the problem of therapeutic heart targeting with use of nanoparticles. Experimental approaches included fabrication of carbon and silica nanoparticles, their characterization and surface modification. The acute hemodynamic effects of nanoparticle formulation as well as nanoparticle biodistribution were studied in male Wistar rats. Carbon and silica nanoparticles are nontoxic materials that can be used as carriers for heart-targeted drug delivery. Concepts of passive and active targeting can be applied to the development of targeted drug delivery to the ischemic myocardial cells. Provided that ischemic heart-targeted drug delivery can be proved to be safe and efficient, the results of this research may contribute to the development of new technologies in the pharmaceutical industry.

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

“…The liver was chosen for sampling and analysis on the basis of previous biodistribution experiments showing maximal accumulation of silica in this organ. 12 Quantitative analysis of silicon content within the samples was performed using atomic absorption spectroscopy. The product of mineralization obtained after drying was analyzed by atomic absorption spectrometry with electrothermic atomization and Zeeman correction.…”

“…We have previously shown that 6-13 nm silica nanoparticles are not toxic during acute intravenous administration and can also be readily functionalized by immobilization or chemical assembly approaches. 12 Although recent research has made signif icant strides in clarifying the mechanisms of endogenous and pharmacological cardioprotection, we still do not have an "ideal" cardioprotective agent with a favorable safety and efficacy profile. There is now considerable evidence for involvement of adenosine in the mechanism(s) of ischemic postconditioning-induced cardiac protection.…”

In vitro biocompatibility of calcined mesoporous silica particles and fetal blood cells

“…Their engulfment occurred without a need for surface activation by organic or polymeric groups, as previously reported for similar materials in other tissues. 9,10,20,[29][30][31] Uptake was likely mediated by the high affinity of phospholipids in the plasma membrane for particle surface groups, such as silanols and silanolate. 25,[32][33][34] The TEM images (Figures 2 and 3, and Figures S1 and S2) show that MCM41-cal and SBA15-cal are distributed in different cellular compartments and are abundant in macrophages.…”

Cardiac Protection with Targeted Drug Delivery to Ischemic-Reperfused Myocardium

“…In our studies, the standard pyrogenic highly dispersed silica (Aerosil A380 mark obtained from Vekton, Russia) was used throughout experiments. Surface area of silica nanoparticles was determined with use of Brunauer-Emmett-Teller (BET) method and averaged from 170 to 380 m 2 /g (Galagudza et al, 2010). The mean particle diameter varied from 6 to 13 nm.…”