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The Investigation Of Novel Anticoagulant Material Composed Of Ions And Heparin

Posted on:2008-11-28Degree:MasterType:Thesis
Country:ChinaCandidate:L YuFull Text:PDF
GTID:2144360245496739Subject:Genetics
Abstract/Summary:PDF Full Text Request
A novel type of heparin functionalized microcapsule had been developed by means of alternating deposition of oppositely charged polyelectrolytes. In our studies, we used heparin, an anticoagulant agent, to prepare nano-scale hollow capsule with layer-by-layer self-assembly method. The layer-by-layer coating process was monitored by microelectrophoresis. Microcapsule morphology and size were analysed using confocal laser scanning microscopy (CLSM) and atomic force microscope (AFM). The thickness of microcapsule wall was 6.49±0.90 nm. To test the bioactivity of microcapsule, the value of activated partial thromboplastin time (APTT) was assessed compared with the standard curve of heparin in vitro. The anticoagulant activity of microcapsule was 95.7 U/mg. The self-assembly technique provides a simple and efficient way to construct a required and uniform thickness, irrespective of the microcapsule shape and a stable film. The contact angle, percent hemolysis test and platelet adhesion assay demonstrate a significantly improved hemocompatibility. The dynamic light scattering (DLS) and Zeta-potential results showed that the average diameter and surface charge of the microcapsule were 901.6±10.5 nm and-48.6±0.82 mV, respectively. After injection of heparin functionalized microcapsules in rats, the time course of modification of the clotting time estimated by the APTT was followed for 12 hours. Compared with the same dosage of heparin, heparin functionalized microcapsule displayed a prolongation of action characterized by a twofold increase (lasted 9-10 hours) in APTT after intravenous injection. This study suggested heparin functionalized microcapsule developed heparin into a new anticoagulant dosage and has great potential to be widely used as an anticoagulant agent replacing heparin, maintaining the plasma concentration in the therapeutic window, and as a long-circulating drug reservoir.
Keywords/Search Tags:anticoagulant, heparin, layer by layer self-assembly, microcapsules, long circulating carrier
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