An Evaluation of the in vivo Safety of Nonporous Silica Nanoparticles: Ocular Topical Administration versus Oral Administration.

Nonporous silica nanoparticles (SiNPs) have potential as promising carriers for ophthalmic drugs. However, the in vivo safety of ocular topical SiNPs remains unclear. This study investigated the in vivo safety of oral and ocular topical applications of 100 nm-sized SiNPs in Sprague-Dawley rats. The rats were divided into the following four groups: low-dose oral administration (total 100 mg/kg of SiNPs mixed with food for one week), high-dose oral administration (total 1000 mg/kg of SiNPs mixed with food for one week), ocular topical administration (10 mg/ml concentration, one drop, applied to the right eyes four times a day for one month), or a negative control (no SiNP treatment). The rats were observed for 12 weeks to investigate any signs of general or ocular toxicity. During the observation period, no differences were observed in the body weights, food and water intakes, behaviors and abnormal symptoms of the four groups. No animal deaths occurred. After 12 weeks, hematologic, blood biochemical parameters and ophthalmic examinations revealed no abnormal findings in any of the animals. The lack of toxicity of the SiNPs was further verified in autopsy findings of brain, liver, lung, spleen, heart, kidneys, intestine, eyeballs, and ovaries or testes.

Investigation of T2-weighted signal intensity of infarcted myocardium and its correlation with delayed enhancement magnetic resonance imaging in a porcine model with reperfused acute myocardial infarction.

To assess the signal pattern in T2-weighted images (T2WI) and determine its relation to persistent microvascular obstruction (PMO) and intramyocardial hemorrhage in a porcine model with reperfused acute myocardial infarction. Left anterior descending artery was occluded (90 or 180 min) and reperfused (90 min). T2WI and delayed-enhanced magnetic resonance images (DE-MRI) were acquired. The T2WI signal pattern, T2WI contrast ratio, PMO, and intramyocardial hemorrhage were evaluated, and their interrelationships were analyzed. The infarct area on T2WI was recorded as a homogeneous high-intensity signal or as low- or iso-intensity signals. The contrast ratio of the T2WI in the cases with PMO was significantly lower than that in those without PMO (1.38 +/- 0.25 vs. 1.89 +/- 0.31, P < 0.05), and it showed significant inverse correlation with the extent of PMO observed in DE-MRI images (r =-0.8, P < 0.05). The extent of PMO correlated strongly with that of intramyocardial hemorrhage (r = 0.97, P < 0.05). The abnormal signal area in the T2WI was larger than the infarct area in the DE-MRI images (47.0 +/- 9.9% vs. 37.8 +/- 9.9%, P < 0.05) and the infarct area observed after TTC staining (47.0 +/- 9.9% vs. 37.4 +/- 8.4%, P < 0.05). We observed variable T2WI signal patterns for the infarcted myocardium. Lower T2WI contrast ratios significantly correlated with the extent of PMO in DE-MRI and intramyocardial hemorrhage in the gross specimen.