Synthesis of chitosan iodoacetamides via carbodiimide coupling reaction: Effect of degree of substitution on the hemostatic properties

Abstract Uncontrolled hemorrhage continues to be the leading cause of death from traumatic injuries both in the battlefield and in the civilian life. Chitosan is among the very few materials that have made the short list of military recommended field-deployable hemostatic dressings. However, the detailed mechanism of its action is still not fully understood. Moreover, in the cases when patients developed coagulopathy, the efficacy of the dressings rely solely on those mechanisms that work outside of the regular blood coagulation cascade. In addition to the well-known erythrocyte agglutination, we proposed to use the reactive N-iodoacetyl group on a new chitosan derivative to accelerate hemostasis. In this paper, we describe the synthesis of chitosan iodoacetamide (CI) with considerations of the stoichiometry among the reagents, the choice of solvent, the pH of the reaction medium, and the reaction time. The reaction was confirmed by FT-IR, 1H and 13C NMR, elemental analysis, iodine content analysis, and SEM-EDS. Water contact angle measurements and Erythrocyte Sedimentation Rate (ESR) method were used to evaluate the hemostatic potential of the newly synthesized CI as a function of their degree of substitution (DS). The range of DS was 5.9% to 27.8% for CI. The mid-range of DS gave the best results for the ESR. CIs exhibit favorable cytocompatibilities up to DS 18.7 compared to the generic unmodified chitosan. In general, the biocompatibility of chitosan iodoacetamide slightly declined with increasing the iodide content up to DS 21.5 owing to its affinity to SH groups of cells.