An aminocaproic acid-grafted chitosan derivative with superior antibacterial and hemostatic properties for the prevention of secondary bleeding

Abstract

Uncontrolled bleeding is one of the leading causes of human mortality. Existing hemostatic materials or techniques cannot meet the clinical requirements for safe and effective hemostasis. The development of novel hemostatic materials has always been of great interest. Chitosan hydrochloride (CSH), a derivative of chitin, is extensively used on wounds as an antibacterial and hemostatic agent. However, the formation of intra- or intermolecular hydrogen bonds between hydroxyl and amino groups limits its water solubility and dissolution rate and affects its effectiveness in promoting coagulation. Herein, we covalently grafted aminocaproic acid (AA) to the hydroxyl and amino groups of CSH via ester and amide bonds, respectively. The solubility of CSH in water (25 °C) was 11.39 ± 0.98 % (w/v), whereas the AA-grafted CSH (CSH-AA) reached 32.34 ± 1.23 % (w/v). Moreover, the dissolution rate of CSH-AA in water was 6.46 times higher than that of CSH. Subsequent studies proved that CSH-AA is non-toxic, biodegradable, and has superior antibacterial and hemostatic properties to CSH. Additionally, anti-plasmin activity can be exerted by the dissociated AA from the CSH-AA backbone, which can help to lessen secondary bleeding.

Keywords: Aminocaproic acid; Bleeding; Chitosan derivative; Dissolution rate; Hemostatic materials; Solubility.