Inactivation of Heparin by Cationically Modified Chitosan

Abstract

This study was performed to evaluate the ability of N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC), the cationically modified chitosan, to form biologically inactive complexes with unfractionated heparin and thereby blocking its anticoagulant activity. Experiments were carried out in rats in vivo and in vitro using the activated partial thromboplastin time (APTT) and prothrombin time (PT) tests for evaluation of heparin anticoagulant activity. For the first time we have found that HTCC effectively neutralizes anticoagulant action of heparin in rat blood in vitro as well as in rats in vivo. The effect of HTCC on suppression of heparin activity is dose-dependent and its efficacy can be comparable to that of protamine-the only agent used in clinic for heparin neutralization. HTCC administered i.v. alone had no direct effect on any of the coagulation tests used. The potential adverse effects of HTCC were further explored using rat experimental model of acute toxicity. When administered i.p. at high doses (250 and 500 mg/kg body weight), HTCC induced some significant dose-dependent structural abnormalities in the liver. However, when HTCC was administered at low doses, comparable to those used for neutralization of anticoagulant effect of heparin, no histopathological abnormalities in liver were observed.

Preparation and in vivo evaluation of surface heparinized small diameter tissue engineered vascular scaffolds of poly(ε-caprolactone) embedded with collagen suture

“…41 Limited cell infiltration often delays and even prevents the regeneration and remodeling progress of vascular grafts in the latter term. 28 In the present study, benefiting from the surface heparinization of PCL through H 2 N–PEG–NH 2 featured by a hierarchical double electrospun microfiber structure, and increased hydrophilicity and biodegradation rate, CCK8 assay clearly revealed that the surface heparinized electrospun PCL vascular scaffolds indeed supported the adhesion and proliferation of ECs and SMCs. As discussed above, the surface heparinization endowed the grafts with improved hydrophilicity as well as the significantly modified morphology.…”

“…20 Heparin is a natural anticoagulant substance and has a long safe history for use in the thromboembolic diseases, myocardial infarction, cardiovascular surgery, cardiopulmonary bypass, cardiac catheterization, hemodialysis access for end-stage renal disease, and so on. [26][27][28] Heparin molecule contains many anionic groups, such as sulfonic acid group (-SO 3 H) and carboxyl group (-COOH), so it is a natural hydrophilic polysaccharide having strong negative electricity. 29 This structural feature enables it holding great promise to enhance vascular TE through its ability to prevent vascular clogging and adsorb growth factor and other peptide molecules to realize cell adhesion and proliferation through electrostatic interaction substantially facilitating endothelialization and regulate proliferation and differentiation of SMCs ultimately.…”

An Overview of Current Knowledge on the Properties, Synthesis and Applications of Quaternary Chitosan Derivatives

“…In addition, HTCC forms smaller aggregates with heparin and with less polydispersity, which can be advantageous in medical procedures, such as intravenous applications. Lorkowska-Zawicka et al [163] evaluated the aforementioned results with applications in rats in vivo and in rats' blood in vitro, and observed that the reversal action of heparin is maintained under the conditions evaluated, safely and without toxic effects when administered in doses adjusted for complexation with heparin.…”

Lost in (Clinical) Translation: Recent Advances in Heparin Neutralization and Monitoring

“…In addition, the polymer was rapidly eliminated (half-life of 12.5 ± 3.0 minutes) without any blood and organ toxicity. 37 The polymeric backbone of antidotes can also be fully synthetic, such as in PAH (poly(allylamine hydrochloride)). Directly inspired by protamine, a PAH polymer on which 9% of the amino groups were replaced by arginine was tested as heparin antagonist.…”