Preparation of ethylene glycol chitosan-diethylenetriamine pentaacetic acid and assessment for its relative safety

Abstract

Objective To synthesize ethylene glycol chitosan-diethylenetriamine pentaacetic acid (GC-DTPA), and evaluate its cytocompatibility and systemic toxicity within the dose range of routine use. Methods DTPA was grafted onto ethylene glycol chitosan (GC) by organic synthesis and chemical cross-linking method, and was subsequently characterized with proton nuclear magnetic resonance (1H NMR) and Fourier transform infrared (FT-IR) spectroscopy. CCK-8 assay was used to detect the effects of different concentrations of GC-DTPA on the proliferation of ICE-6 cells. In addition, 80 healthy SPF SD rats (aged 6~8 weeks, body weight 180~220 g) were randomly divided into 4 groups (n=20): control group (given normal saline), and experimental groups (60, 90 and 120 mg/kg GC-DTPA, respectively by intragastric gavage). The change of body weight and survival rate of rats in each group were observed. Blood routine test and blood biochemical examination were performed in the rats on the 14th day after gavage with aid of automatic blood humoral and biochemical immunoassay analyzers respectively. Then, the rats were sacrificed and the pathological changes of organs were observed after HE staining. Results FT-IR spectroscopy and 1H-NMR suggested that DTPA was successfully grafted onto GC, and GC-DTPA exhibited excellent cytocompatibility, with cell viability all above 90% after its treatment at different concentrations. In 14 d after administration, no significant differences were seen in the results of blood routine and blood biochemical tests, or in pathological changes of organs and tissues in each group. Conclusion The GC-DTPA synthesized by chemical synthesis and cross-linking method shows no obvious cytotoxicity, and no systemic toxicity is seen even after oral administration dose up to 120 mg/kg

Keywords

• chitosan
• diethylenetriamine pentaacetic acid
• cytocompatibility
• systemic toxicity