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生物共轭链激酶-聚甘油树枝状大分子的抗血栓形成特性。

Antithrombogenic properties of bioconjugate streptokinase-polyglycerol dendrimers.

作者信息

Fernandes Edson Giuliani Ramos, de Queiroz Alvaro Antonio Alencar, Abraham Gustavo A, San Román Julio

机构信息

Departamento de Física e Química, Instituto de Ciências Exatas, Universidade Federal de Itajubá (UNIFEI), Av. BPS. 1303, 37500-903, Itajubá, Minas Gerais, Brasil.

出版信息

J Mater Sci Mater Med. 2006 Feb;17(2):105-11. doi: 10.1007/s10856-006-6813-5.

DOI:10.1007/s10856-006-6813-5
PMID:16502242
Abstract

Dendrimers are monodisperse, spherical and hyperbranched synthetic macromolecules with a large number of surface groups that have the potential to act as carriers for drug immobilization by covalent binding or charge transfer complexation. In this work, a bioconjugate of streptokinase and a polyglycerol dendrimer (PGLD) generation 5 was used to obtain fibrinolytic surfaces. The PGLD dendrimer was synthesized by the ring opening polymerization of deprotonated glycidol using polyglycerol as core functionality in a step-growth processes denominated divergent synthesis. The PGLD dendritic structure was confirmed by gel permeation chromatography (GPC), nuclear magnetic resonance (1H-NMR, 13C-NMR) and matrix assisted laser desorption/ionization (MALDI-TOF) techniques. The synthesized dendrimer presented low dispersion in molecular weights (Mw/Mn = 1.05) and a degree of branching of 0.82 which characterize the polymer dendritic structure. The blood compatibility of the bioconjugate PGLD-Sk was evaluated by in vitro assays such as platelet adhesion and thrombus formation. Uncoated polystyrene -microtitre plates (ELISA) was used as reference. The epifluorescence microscopy results indicate that PGLD-Sk coating showed an improved antithrombogenic character relative to the uncoated ELISA plates.

摘要

树枝状聚合物是单分散、球形且高度支化的合成大分子,带有大量表面基团,有可能通过共价结合或电荷转移络合作用作为药物固定的载体。在这项工作中,使用链激酶与第5代聚甘油树枝状聚合物(PGLD)的生物共轭物来获得纤溶表面。PGLD树枝状聚合物是通过以聚甘油为核心官能团,使去质子化的缩水甘油开环聚合,在一种称为发散合成的逐步增长过程中合成的。PGLD树枝状结构通过凝胶渗透色谱法(GPC)、核磁共振(1H-NMR、13C-NMR)和基质辅助激光解吸/电离(MALDI-TOF)技术得到证实。合成的树枝状聚合物在分子量方面呈现出低分散性(Mw/Mn = 1.05)以及0.82的支化度,这些特性表征了聚合物的树枝状结构。通过血小板黏附和血栓形成等体外试验评估了生物共轭物PGLD-Sk的血液相容性。未包被的聚苯乙烯微量滴定板(ELISA)用作对照。落射荧光显微镜结果表明,相对于未包被的ELISA板,PGLD-Sk包被显示出改善的抗血栓形成特性。

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