Monfared Yousef Khazaei, Mahmoudian Mohammad, Hoti Gjylije, Bisericaru Daniel Mihai, Caldera Fabrizio, Cavalli Roberta, Zakeri-Milani Parvin, Matencio Adrián, Trotta Francesco
Dipartimento di Chimica and NIS, Università di Torino, Via P. Giuria 7, 10125 Torino, Italy.
Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz 5166-15731, Iran.
Bioengineering (Basel). 2022 Dec 4;9(12):765. doi: 10.3390/bioengineering9120765.
This study tested the anticoagulant effect of cyclodextrin (CD) hyper-branched-based polymers (HBCD-Pols). These polymers were synthesized and tested for their coagulant characteristics in vitro and in vivo. Due to their polymeric structure and anionic nature, the polymers can chelate Ca, reducing the free quantity in blood. HBCD-Pol increased the blood clotting time, PT, and aPTT 3.5 times over the control, showing a better effect than even ethylenediaminetetraacetic acid (EDTA), as occured with recalcification time as well. A titration of HBCD-Pol and EDTA showed exciting differences in the ability to complex Ca between both materials. Before executing in vivo studies, a hemocompatibility study was carried out with less than 5% red blood cell hemolysis. The fibrinogen consumption and bleeding time were analyzed in vivo. The fibrinogen was considerably decreased in the presence of HBCD-Pol in a higher grade than EDTA, while the bleeding time was longer with HBCD-Pols. The results demonstrate that the anticoagulant effect of this HBCD-Pol opens novel therapy possibilities due to the possible transport of drugs in this carrier. This would give combinatorial effects and a potential novel anticoagulant therapy with HBCD-Pol per se.
本研究测试了基于环糊精(CD)超支化聚合物(HBCD-Pols)的抗凝效果。合成了这些聚合物,并在体外和体内测试了它们的凝血特性。由于其聚合物结构和阴离子性质,这些聚合物可以螯合钙,减少血液中的游离钙量。HBCD-Pol使血液凝固时间、PT和活化部分凝血活酶时间(aPTT)比对照组延长了3.5倍,甚至比乙二胺四乙酸(EDTA)的效果更好,再钙化时间也是如此。HBCD-Pol和EDTA的滴定显示出两种材料在螯合钙能力上令人兴奋的差异。在进行体内研究之前,进行了红细胞溶血率低于5%的血液相容性研究。在体内分析了纤维蛋白原消耗和出血时间。在HBCD-Pol存在的情况下,纤维蛋白原的降低程度比EDTA更高,而HBCD-Pols的出血时间更长。结果表明,这种HBCD-Pol的抗凝作用由于药物可能在该载体中运输而开辟了新的治疗可能性。这将产生协同效应,并可能带来一种基于HBCD-Pol本身的新型抗凝疗法。