Heparin polyelectrolyte nature

Polydispersity of molecular weights of heparin was recognized in early studies (reviewed in Refs. 9 and 183). However, the polyelectrolyte nature and heterogeneity of charge distribution have hampered accurate determinations of molecular-weight distribution. 

Heparin has been used in medicine and surgery for nearly 40 years and in this time has maintained a well-earned reputation as an effective and safe drug [1]. I may claim a share in this as I was a member of the research team at the University of Toronto which developed heparin for clinical use. The major clinical uses of heparin are for the prevention of thrombosis and the prevention of clotting of blood. Thrombosis is the complex plugging of blood vessels which can occur in veins after operation and child-birth and can occur in arteries as the result of diet, age and stress. Clotting of blood is a serious problem in the use of heart-lung machines, artificial kidneys, etc. and the prevention of this by heparin is most important. My presentation reviews points about this drug which indicates its actions are due to its polyelectrolyte nature. 

The polyelectrolyte nature of heparin has significance for determinations of its molecular weight. We have seen that molecular weight estimations are not practical by oncotic measurements. Measureable viscosity can be due to accompanying protein or polysaccharide. In my experience, viscous polysaccharide can be produced during the extraction procedure and traces of these can be responsible for considerable viscosity. The sites of ion binding and problems of double decomposition means that... 

Problems of desorption and loss of activity encountered with natural heparin have led numerous workers to explore synthetic heparin-like polymers or heparinoids, as reviewed by Gebelein and Murphy [475, 514, 515]. The blood compatibility of 5% blended polyelectrolyte/polyfvinly alcohol) membranes was studied by Aleyamma and Sharma [516,517]. The membranes were modified with synthetic heparinoid polyelectrolytes, and surface properties (platelet adhesion, water contact angle, protein adsorption) and bulk properties such as permeability and mechanical characteristics were evaluated. The blended membrane had a lower tendency to adhere platelets than standard cellulose membranes and were useful as dialysis grade materials. 

Electrostatic polyelectrolyte complexes (PEC) are mentioned in the literature involving chitosan and synthetic or natural polymers such as PAA and CMC [155,156], xanthan, carrageenan, alginate [157-162], pectin [163,164], heparin, hyaluronan (HA) [165-169], sulfated cellulose, dextran sulfate, or N-acylated chitosan/chondroitin sulfate. Many systems were cited in the literature [2, 170]. The electrostatic interaction was discussed in relation with the stiffness of the backbone and the nature of the ionic groups involved. Especially, with alginate or HA, a pH-dependent complex is formed, whose stability depends on the ionic concentration. The complex formation was investigated in dilute solution by potentiometry (pH) and conductivity to determine the fraction of ion pairs (-COO + NH3 —) formed in dependence of the experimental conditions [164, 166]. 

The second part describes recent information on the properties and biological effects of already well-known natural polyelectrolytes such as heparin and DNA and recently developed polymers such as pyran and polyionenes. The effects of polyanions and polycations on normal and transformed cells as well as on acetylcholine receptors follow. This part is of particular interest to scientists involved in biological research. 

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