Effect of Biopolymers and Functionalized by Them Vaterite Microparticles on Platelet Aggregation

IF 0.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
D. V. Grigorieva, E. V. Mikhalchik, N. G. Balabushevich, D. V. Mosievich, M. A. Murina, O. M. Panasenko, A. V. Sokolov, I. V. Gorudko
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Abstract

Vaterite microparticles, metastable form of calcium carbonate, are promising forms of delivery of medicinal compounds. For more efficient delivery of target molecules (increased incorporation and retention), vaterite microparticles must be functionalized with biopolymers. In this article the effect of polysaccharides, mucin and vaterite microparticles, as well as hybrid vaterite microparticles with the above-mentioned biopolymers was studied on platelet aggregation. It was found that fucoidan, heparin and dextran sulfate (when added to platelet-rich plasma) and mucin (when added to isolated platelets) initiated cell aggregation. Pectin and chondroitin sulfate inhibited ADP- and thrombin-induced aggregation in a dose-dependent manner, mucin suppressed ADP-induced, and dextran sulfate suppressed thrombin-induced platelet aggregation. Vaterite microparticles at a concentration of 100–1000 µg/mL did not affect the aggregation of isolated platelets, but caused 10–15% cell aggregation in plasma; at the same time, at a concentration of 1000 µg/mL vaterite microparticles prevented agonist-induced cell aggregation by ~30%. It has been established that hybrid vaterite microparticles with fucoidan or heparin, when added both to platelet-rich plasma and to isolated cells, are capable to initiate platelet aggregation. Vaterite microparticles functionalized with pectin or chondroitin sulfate had no effect on spontaneous cell aggregation, and did not affect (with chondroitin sulfate) or inhibit (with pectin) agonist-induced platelet aggregation. Thus, the use of hybrid vaterite microparticles with pectin or fucoidan/heparin may be promising for the delivery of drugs aimed at modulating (inhibition with pectin or activation with fucoidan/heparin) the platelet component of hemostasis.

Abstract Image

生物聚合物和功能化毛细管微粒对血小板聚集的影响
摘要 大理石微颗粒是碳酸钙的蜕变形式,是一种很有前景的药物输送形式。为了更有效地递送目标分子(提高结合率和保留率),必须用生物聚合物对大孔岩微颗粒进行功能化。本文研究了多糖、粘蛋白和醋酸盐微颗粒以及含有上述生物聚合物的混合醋酸盐微颗粒对血小板聚集的影响。研究发现,褐藻糖胶、肝素和硫酸葡聚糖(加入富血小板血浆中)以及粘蛋白(加入离体血小板中)会引发细胞聚集。果胶和硫酸软骨素以剂量依赖的方式抑制 ADP 和凝血酶诱导的聚集,粘蛋白抑制 ADP 诱导的聚集,硫酸葡聚糖抑制凝血酶诱导的血小板聚集。浓度为 100-1000 µg/mL 的 Vaterite 微颗粒不会影响离体血小板的聚集,但会导致血浆中 10-15% 的细胞聚集;同时,浓度为 1000 µg/mL 的 Vaterite 微颗粒可防止拮抗剂诱导的细胞聚集约 30%。研究证实,在富含血小板的血浆和离体细胞中加入含有褐藻糖胶或肝素的杂交aterite 微颗粒,能够引发血小板聚集。用果胶或硫酸软骨素功能化的aterite 微颗粒对自发细胞聚集没有影响,也不影响(用硫酸软骨素)或抑制(用果胶)激动剂诱导的血小板聚集。因此,使用含有果胶或褐藻糖胶/肝素的混合型沃特来特微粒可能很有前景,可用于递送旨在调节(用果胶抑制或用褐藻糖胶/肝素激活)止血血小板成分的药物。
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来源期刊
自引率
33.30%
发文量
110
审稿时长
6-12 weeks
期刊介绍: Journal of Evolutionary Biochemistry and Physiology  publishes original experimental and theoretical and review articles related to evolution of the main forms of metabolism in connection with life origin; comparative and ontogenetic physiology and biochemistry, biochemical evolution of animal world; as well as evolution of functions; morphology, pharmacology, pathophysiology and ecological physiology. The journal welcomes manuscripts from all countries in the English or Russian language.
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