Mîndrilă Bogdan, Buteică Sandra-Alice, Mîndrilă Ion, Mihaiescu Dan-Eduard, Mănescu Marina-Daniela, Rogoveanu Ion
Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania.
Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania.
Biomedicines. 2022 May 23;10(5):1213. doi: 10.3390/biomedicines10051213.
The liver is a key organ in the pharmacokinetics of iron oxide nanoparticles (IONPs). This paper examined how the intravenous (IV) or intragastric (IG) route of administration influenced the intrahepatic distribution or therapeutic effects of IONPs. Wistar rats, some with bleeding-induced anemia, and iron oxide nanoparticles functionalized with salicylic acid (SaIONPs), with an average hydrodynamic diameter of 73 nm, compatible with rat sinusoid fenestrations, were used in this study. Light microscopy and multispectral camera analysis of Prussian blue labeled SaIONPs allowed mapping of intrahepatic nanoparticle deposits and revealed intrahepatic distribution patterns specific to each route of administration: loading of Kupffer cells and periportal hepatocytes when the IV route was used and predominant loading of hepatocytes when the IG route was used. Reducing the time to return to baseline values for hemoglobin (HGB) in rats with bleeding-induced anemia with IV or IG therapy has proven the therapeutic potential of SaIONPs in such anemias. The long-term follow-up showed that IV therapy resulted in higher HGB values. Proper use of the administration routes may modulate intrahepatic distribution and therapeutic effects of nanoparticles. These results may be beneficial in theragnosis of liver disease.
肝脏是氧化铁纳米颗粒（IONPs）药代动力学中的关键器官。本文研究了静脉注射（IV）或胃内给药（IG）途径如何影响IONPs在肝内的分布或治疗效果。本研究使用了Wistar大鼠，其中一些患有出血性贫血，并使用了平均流体动力学直径为73 nm、与大鼠窦状隙窗孔相适配的水杨酸功能化氧化铁纳米颗粒（SaIONPs）。对普鲁士蓝标记的SaIONPs进行光学显微镜和多光谱相机分析，可绘制肝内纳米颗粒沉积物图谱，并揭示每种给药途径特有的肝内分布模式：静脉注射途径使用时库普弗细胞和门静脉周围肝细胞的负载，以及胃内给药途径使用时肝细胞的主要负载。通过静脉注射或胃内给药疗法缩短出血性贫血大鼠血红蛋白（HGB）恢复到基线值的时间，已证明SaIONPs在这类贫血中具有治疗潜力。长期随访表明，静脉注射疗法导致更高的HGB值。合理使用给药途径可能会调节纳米颗粒在肝内的分布和治疗效果。这些结果可能对肝病的诊疗有益。
