ГЕМОСОВМЕСТИМОСТЬ N-КАРБОКСИАЦИЛЬНЫХ ПРОИЗВОДНЫХ ХИТОЗАНА

Abstract

Objective. To determine hemocompatibility of N-succinyl-chitosan (SC) and N-glutaryl-chitosan (GC). Materials and methods. Effect of SC and GC on the vascular-platelet hemostasis (adhesion and agonist-induced aggregation) and anticoagulation properties (APTT, PT and TT) of SC and GC was evaluated with donor blood. The acute toxicity of SC and GC was evaluated on anesthetized rats, which was subjected to intravenous administration of 1 % solutions of SC and GC. The effect on systemic hemodynamics and the presence of hemolysis was evaluated. Cell viability assay (MTT-test) in the presence of SC and GC was carried out with HL-1 cell line for evaluation of cytotoxic potential of chitosan derivatives. Results. Intravenous administration of aqueous solutions of SC and GC (molecular weight 83,000, deacetylation degree 0.93) in acute experiments on anesthetized rats did not cause hemolysis, changes in the parameters of systemic hemodynamics and respiratory rate. The data from the platelet aggregation assays and the coagulation assays with human blood indicate that chitosan derivatives possess anticoagulant and antiplatelet properties. In the test for cytotoxicity (MTT-test) addition of SC (degree of substitution 0.85) in cell medium did not affect the viability of HL-1 cell culture within 3 days of incubation, while GC (degree of substitution 0.71) showed toxic effect after cell exposure to different concentrations (0,1 %, 0,01 % и 0,001 %) of the one after two days of incubation. Conclusion. The results show the low toxicity of SC and possibility of its use in biomedical applications and in the development on its base parenteral formulations. The observed toxicity of GC does not allow to recommend its parenteral administration. However, given the lack of influence of GC on the systemic hemodynamics, further modification of the GC is needed to reduce the effects on platelet function and cell viability.