DEAE/Catechol-Chitosan Conjugates as Bioactive Polymers: Synthesis, Characterization, and Potential Applications.

ABSTRACT

This work provides the first description of the synthesis and characterization of water-soluble chitosan (Cs) derivatives based on the conjugation of both diethylaminoethyl (DEAE) and catechol groups onto the Cs backbone (Cs-DC) in order to obtain a Cs derivative with antioxidant and antimicrobial properties. The degree of substitution [DS (%)] was 35.46% for DEAE and 2.53% for catechol, determined by spectroscopy. Changes in the molecular packing due to the incorporation of both pendant groups were described by X-ray diffraction and thermogravimetric analysis. For Cs, the crystallinity index was 59.46% and the maximum decomposition rate appeared at 309.3 °C, while for Cs-DC, the values corresponded to 16.98% and 236.4 °C, respectively. The incorporation of DEAE and catechol groups also increases the solubility of the polymer at pH > 7 without harming the antimicrobial activity displayed by the unmodified polymer. The catecholic derivatives increase the radical scavenging activity in terms of the half-maximum effective concentration (EC50). An EC50 of 1.20 µg/mL was found for neat hydrocaffeic acid (HCA) solution, while for chitosan-catechol (Cs-Ca) and Cs-DC solutions, concentrations equivalent to free HCA of 0.33 and 0.41 µg/mL were required, respectively. Cell culture results show that all Cs derivatives have low cytotoxicity, and Cs-DC showed the ability to reduce the activity of reactive oxygen species by 40% at concentrations as low as 4 µg/mL. Polymeric nanoparticles of Cs derivatives with a hydrodynamic diameter (Dh) of around 200 nm, unimodal size distributions, and a negative ζ-potential were obtained by ionotropic gelation and coated with hyaluronic acid in aqueous suspension, providing the multifunctional nanoparticles with higher stability and a narrower size distribution.