Synthesis of N-succinyl- and N-glutaryl-chitosan derivatives and their antioxidant, antiplatelet, and anticoagulant activity.

The effects of temperature, reactant ratio, pH, and reaction time were studied on the polymers formed by the reactions of succinic and glutaric anhydrides with chitosan under both homogeneous and heterogeneous conditions. As a result, protocols were developed for the synthesis of succinyl- and glutaryl-chitosan derivatives (SC and GC, respectively) with a specific degree of substitution. The polymers were characterized by NMR spectroscopy, including two-dimensional NMR techniques, that confirms N-substitution of chitosan under reaction conditions used. SC and GC both show pronounced and similar antioxidant activity, which slightly increases with an increase in the degree of substitution. Both SC and GC showed antiplatelet and anticoagulant activity. The platelet aggregation is suppressed more strongly in the experiments with GC than with SC, although the latter exhibits a more pronounced anticoagulant activity.

Development of drug delivery systems for taxanes using ionic gelation of carboxyacyl derivatives of chitosan.

Nanoparticles of two chitosan derivatives - N-succinyl-chitosan (SC) and N-glutaryl-chitosan (GC) - were developed as passive transport systems for taxanes (paclitaxel and docetaxel) using an ionic gelation technique with sodium tripolyphosphate. These nanoparticles had an apparent hydrodynamic diameter of 300-350nm, a ζ-potential of 25-31mV, an encapsulation efficiency of 21-26%, and a drug loading efficiency of 6-13%. DLS and SLS analysis shows that the nanoparticles have a unimodal size distribution and spherical form. Drug release kinetics of the taxane-loaded nanoparticles demonstrates that more than 50% of the loaded taxane could be released upon the degradation of the nanoparticles after targeted delivery. The drug-loaded SC and GC nanoparticles exhibit high cytotoxicity towards AGS cancer cell lines and their antitumor activity is consequently enhanced when compared with free taxanes.