Heparin, Heparinoids, Synthetic Polyanions, and Anionic Dyes

Abstract

Review of native heparin action provides new applica tions for synthetic polyanions. Furor over dextran sulfate or suramin, anionic dyes as anti-AIDS or anti-tumor drugs forgets the past history of polyanions: As physicochemical combinants, reverse transcriptase inhibitors and immunoadjuvants. This goes back to Ehrlich and anionic dyes, S. S. Cohen and heparin, ethylene maleic anhydride copolymers, and the macroanionic tungstates and heteropolymolybdates. Unfortunately, in this AIDS era, vaccine enhancing action of the polycarboxylate polymers Diveema (MVE, pyran copolymer) is still ignored. Their clinically effective anti-tumor potential requires intraperitoneal not intravenous use. Preclinical experience with newer sulfated native glycosaminoglycan heparin fractions should re-evaluate the place of synthetic polyanions for anti coagulant, lipolytic (anti-atherosclerosis action), anti -inflammatory effects and DNA modulation. Inhibition of angio genesis and smooth muscle proliferation via modulation of cytokines as well as oral absorption and endothelial localization provides new roles for polyanions of clinical value.In recent years, there has been a veritable explosion of interest in both native heparin or heparin related, glycosaminoglycans; synthetic polyanions, or anionic dyes. It is the purpose of this review to discuss pertinent observations regarding the structural and physiologic actions of these negatively charged polymers because of new interest in their clinical application, independent of uses involving surface modification of implantable polymers.Since Jaques' (1.2) and Engelberg's (3.4) last reviews, Lane & Lindhal (5) have provided a new text that focuses on heparin related proteoglycans where there are excellent sections discussing structure and function (6), but the text is focussed on the naturally derived compounds and completely ignores the water soluble synthetic polyanions whose development stemmed from these native compounds.