Chitosan derivatives as novel potential heparin reversal agents.

In emergency cases anticoagulant action of heparin needs to be stopped instantaneously, which is usually achieved by intravenous administration of protamine sulfate (PS). However, PS shows many adverse effects. The objective of the present work was to find out if chitosan (Ch) and a cationically modified chitosan, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC), may be applied for heparin reversal. For chitosan the efficiency of unfractionated heparin (UFH) binding decreases with increasing pH while for cationically modified chitosan heparin binding is efficient even for high pH values. Complexation of UFH and low-molecular-weight heparin (LMWH) by cationically modified chitosan in the aqueous solution at pH = 7.4 was studied. Complexes of the modified chitosan with UFH are smaller and of lower dispersity than those with PS. Cationically modified chitosan was found to bind both UFH and LMWH. The complex formation capability of cationically modified chitosan is comparable to that of PS.