Oligoamines conjugated chitosan derivatives: Synthesis, characterization, in vitro and in vivo biocompatibility evaluations

The aim of this study was to synthesize water-soluble chitosan derivatives with good compatibility and multiple amine functionalities for delivery applications. Periodate mediate oxidation was employed to give rise to chitosan with flanking aldehyde groups, onto which oligoamines were conjugated. The polymer structure was confirmed by FT-IR and 1H NMR spectra. These newly synthesized chitosan derivatives displayed high water-solubility. In vitro cell culture experiments using both normal and tumor cell lines indicated that some polymers synthesized herein possess extremely low cytotoxicity even at concentrations as high as 5.0 mg/mL. Depending on amine type, the IC50 values of newly synthesized chitosan derivatives for both cell lines are 3–4 order of magnitude larger than those of branched polyethyleneimine (25 kDa). Concentration/structure-dependent toxicity was observed for both cell lines as well. In vitro hemolysis test using ethylenediamine-conjugated chitosan suggested that this polymer did not elicit any hemolysis at concentrations up to 200 μg/mL. In vivo local inflammation evaluation also revealed the compatibility of this polymer post-intramuscular injection. These functionalized chitosan derivatives are candidate materials to construct particulate or hydrogel formulations for biomedical applications.