Sonin Dmitry, Pochkaeva Evgeniia, Zhuravskii Sergei, Postnov Viktor, Korolev Dmitry, Vasina Lyubov, Kostina Daria, Mukhametdinova Daria, Zelinskaya Irina, Skorik Yury, Naumysheva Elena, Malashicheva Anna, Somov Pavel, Istomina Maria, Rubanova Natalia, Aleksandrov Ilia, Vasyutina Marina, Galagudza Michael
Almazov National Medical Research Centre, Institute of Experimental Medicine, 2 Akkuratova str., 197341 Saint Petersburg, Russia.
Pavlov First Saint Petersburg State Medical University, Laboratory of Biophysics of Blood Circulation, 6-8 L'va Tolstogo str., 197022 Saint Petersburg, Russia.
Nanomaterials (Basel). 2020 Apr 23;10(4):810. doi: 10.3390/nano10040810.
The effect of unmodified chitosan nanoparticles with a size of ~100 nm and a weakly positive charge on blood coagulation, metabolic activity of cultured cardiomyocytes, general toxicity, biodistribution, and reactive changes in rat organs in response to their single intravenous administration at doses of 1, 2, and 4 mg/kg was studied. Chitosan nanoparticles (CNPs) have a small cytotoxic effect and have a weak antiplatelet and anticoagulant effect. Intravenous administration of CNPs does not cause significant hemodynamic changes, and 30 min after the CNPs administration, they mainly accumulate in the liver and lungs, without causing hemolysis and leukocytosis. The toxicity of chitosan nanoparticles was manifested in a dose-dependent short-term delay in weight gain with subsequent recovery, while in the 2-week observation period no signs of pain and distress were observed in rats. Granulomas found in the lungs and liver indicate slow biodegradation of chitosan nanoparticles. In general, the obtained results indicate a good tolerance of intravenous administration of an unmodified chitosan suspension in the studied dose range.
研究了粒径约100 nm且带弱正电荷的未修饰壳聚糖纳米颗粒，以1、2和4 mg/kg的剂量单次静脉注射对大鼠血液凝固、培养心肌细胞的代谢活性、一般毒性、生物分布以及大鼠器官反应性变化的影响。壳聚糖纳米颗粒（CNPs）具有较小的细胞毒性作用，且具有较弱的抗血小板和抗凝作用。静脉注射CNPs不会引起显著的血流动力学变化，在注射CNPs后30分钟，它们主要积聚在肝脏和肺中，不会引起溶血和白细胞增多。壳聚糖纳米颗粒的毒性表现为剂量依赖性的体重增加短期延迟，随后恢复，而在2周的观察期内，未观察到大鼠有疼痛和痛苦的迹象。在肺和肝脏中发现的肉芽肿表明壳聚糖纳米颗粒的生物降解缓慢。总体而言，所得结果表明在研究的剂量范围内，静脉注射未修饰的壳聚糖悬浮液具有良好的耐受性。
