Heparin anticoagulant properties

Methods for preparing heparin-containing polymeric materials by means of ionic and covalent immobilization of heparin on various polymers are surveyed. The data on the biological activity of heparin are discussed as well as the probable mechanisms of thromboresistance enhancement endowed to polymeric materials by this anticoagulant. Some approaches toward an increased efficiency of anticoagulant properties of immobilized heparin are analyzed, and the position of heparin-containing polymers among other biomedical polymers is discussed. 

It seemed reasonable to anticipate that the synergism of these two features (high heparin content and stability of the resultant materials) would result in long-term thromboresistant polymers. The in vivo tests revealed, however, their extremely low thromboresistance as compared to the ionically bound heparin-containing polymers, in particular. The effect is assumed to be caused by a lack of sufficient mobility of the polymer-bound heparin molecules, which prevents the performance of the intrinsic anticoagulant properties of heparin. 

Cationic thiomers are obtained from chitosan by reaction of thioglycolic acid with the primary amino groups in chitosan mediated by EDCCl. Thiomers are useful to formulate oral delivery systems for insulin, calcitonin and heparin. However, carbodiimide treated heparin may lose some of its anticoagulant properties. The potential of chitosan for the oral administration of peptides is also under consideration. ... 

Since its isolation from liver in 1916 by McLean (M9) and the recognition of its blood anticoagulant properties, heparin has undoubtedly been the most widely studied of the acid mucopolysaccharides. Heparin has been found in many tissues, for example, liver, lung, heart, kidney, thymus, blood, and spleen. Histochemical methods have demonstrated the presence of heparin in the mast cells, which are located in connective tissues. Molecular weights of 16,000-20,000 have been suggested (M23, W6) for heparin, but many of the physical methods employed are strongly influenced by the polyelectrolyte character of the molecule. 

Apart from its anticoagulant properties, heparin inhibits the proliferation of vascular smooth muscle cells and is involved in angiogenesis. Heparin also... 

Certainly, one of the most used glycosaminoglycans is heparin, because of its anticoagulant properties. Other glycosaminoglycans or polysaccharides have shown such properties among them, sulfated dextran derivatives and naturally sulfated polysaccharides extracted from algae (fucans) will be discussed further. 

Anticoagulant properties are due to the formation of a complex between heparin and antithrombin (ATIII) heparin increases ATIII activity, inhibiting thrombin, which is responsible for the formation of the clot [8]. Although this complex is already characterized by a weak affinity, the exact mechanism of association between heparin and antithrombin is not exactly known. A multistep protocol of immobilization of heparin on silica beads permitted high-performance chromatographic phases to be obtained. Thus, it has been possible to evidence a slightly stronger affinity of heparin for antithrombin than for thrombin. 

To the first point should be added antisteroid (cortisone, aldosterone), anti-inflammatory, anti-allergic, anticomplement and antihypertensive. Possibly a nomenclature is needed that distinguishes the various biological and therapeutic properties of heparin and heparinoids, as well as adequate standards for heparin-anticoagulant, heparin-CF, heparin-anti-aldosterone, heparin-anti-inflammatory and heparin-antithrombosis. 

Heparin, one of the most widely used blood anticoagulants, is an expensive product. Attempts have been made to prepare a number of synthetic anticoagulants, but none are as nontoxic as heparin. It has been reported that cellulose and starch sulfuric acid esters are toxic, whereas chitin disulfuric acid is less toxic. It has also been reported that the protein moiety of chitin is responsible for the inflammatory response when material containing chitin is injected into tissues of higher animals, whereas pure chitin does not give a detectable response. Dutkiewicz et al. [218] have shown that chitosan exhibits not only a hemostatic effect, but also has anticoagulant properties. Some variation... 

The other bioactive polysaccharide that seemed interesting to be used to produce surface-modified nanoparticles reducing their recognition by the host defense was heparin. Heparin is used as a drug for its anticoagulation properties. Additionally, it is an inhibitor of the complement activation phenomenon [116-118]. It was demonstrated that heparin-coated nanoparticles did not activate the complement system [19, 31, 32] and remained in the blood stream for a longer time compared with nanoparticles, which do not show heparin on the nanoparticle surface [89], Other polysaccharides extracted from mushrooms were found to inhibit the activation process of the complement. They could be alternative polysaccharides to produce nanoparticles with a reduced capacity to activate the complement, such as heparin [119],... 

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