Synthesis and characterization of a biocompatible chitosan-based hydrogel cross-linked via 'click' chemistry for controlled drug release

Int J Biol Macromol. 2017 Sep:102:1-9. doi: 10.1016/j.ijbiomac.2017.04.003. Epub 2017 Apr 2.

Abstract

A chemically cross-linked chitosan-based hydrogel was successfully synthesized through Diels-Alder (DA) reaction and characterized. The final product was obtained after different steps; on the one hand, furan-modified chitosan (Cs-Fu) was synthesized by the reaction of furfural with the free amino groups of chitosan. On the other hand, highlighting the novelty of the present research, maleimide-functionalized chitosan (Cs-AMI) was prepared by the reaction of a maleimide-modified aminoacid with the amino groups of chitosan through amide coupling. The two complementary chitosan derivatives were cross-linked to the final hydrogel network. Both modification reactions were confirmed by FTIR and 1H NMR, obtaining a degree of substitution (DS) of 31% and 26% for Cs-Fu and Cs-AMI, respectively. The as-designed hydrogel was analyzed in terms of microstructure, swelling capacity and rheological behaviour. The hydrogel showed pH-sensitivity, biocompatibility and inhibitory bacterial activity, promising features for biomedical applications, particularly for targeted-drug delivery.

Keywords: Chitosan derivatives; Diels–Alder cross–linking reaction; Drug–delivery system.

MeSH terms

  • Animals
  • Biocompatible Materials / chemical synthesis
  • Biocompatible Materials / chemistry*
  • Biocompatible Materials / toxicity
  • Cell Line
  • Cell Survival / drug effects
  • Chemistry Techniques, Synthetic
  • Chitosan / chemistry*
  • Chloramphenicol / chemistry
  • Chloramphenicol / pharmacology
  • Click Chemistry
  • Delayed-Action Preparations
  • Drug Carriers / chemical synthesis
  • Drug Carriers / chemistry*
  • Drug Carriers / toxicity
  • Escherichia coli / drug effects
  • Furans / chemistry
  • Hydrogels / chemical synthesis
  • Hydrogels / chemistry*
  • Hydrogels / toxicity
  • Maleimides / chemistry
  • Mice
  • Rheology
  • Staphylococcus aureus / drug effects

Substances

  • Biocompatible Materials
  • Delayed-Action Preparations
  • Drug Carriers
  • Furans
  • Hydrogels
  • Maleimides
  • maleimide
  • Chloramphenicol
  • Chitosan
  • furan