N-(furfural) chitosan hydrogels based on Diels–Alder cycloadditions and application as microspheres for controlled drug release

• Published in: Carbohydrate polymers 2015-09, Vol.128, p.220-227
• Main Authors: Montiel-Herrera, Marcelino, Gandini, Alessandro, Goycoolea, Francisco M., Jacobsen, Neil E., Lizardi-Mendoza, Jaime, Recillas-Mota, Maricarmen, Argüelles-Monal, Waldo M.
• Format: Article
• Language: English
• Subjects: Chitosan; Chitosan - chemistry; Click Chemistry; Cycloaddition Reaction; Delayed-Action Preparations - chemistry; Diels–Alder; Furaldehyde - chemistry; Furans; Hydrogels; Hydrogels - chemistry; Magnetic Resonance Spectroscopy; Maleimides - chemistry; Microspheres; Reductive amination; Spectroscopy, Fourier Transform Infrared
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2015.03.052

•Synthesis of N-(furfural) chitosan was simple and carried out in two steps.•N-(furfural) chitosan based hydrogels were produced by Diels–Alder cycloadditions.•Higher degree of furfural substitution produced faster and stronger hydrogels.•Microspheres from FC based hydrogels could be prepared.•Hydrogels from renewable resources can be used to design and produce novel materials. In this study, chitosan was chemically modified by reductive amination in a two-step process. The synthesis of N-(furfural) chitosan (FC) was confirmed by FT-IR and 1H NMR analysis, and the degrees of substitution were estimated as 8.3 and 23.8%. The cross-linkable system of bismaleimide (BM) and FC shows that FC shared properties of furan–maleimide chemistry. This system produced non-reversible hydrogel networks by Diels–Alder cycloadditions at 85°C. The system composed of BM and FC (23.8% substitution) generated stronger hydrogel networks than those of FC with an 8.3% degree of substitution. Moreover, the FC–BM system was able to produce hydrogel microspheres. Environmental scanning electron microscopy revealed the surface of the microspheres to be non-porous with small protuberances. In water, the microspheres swelled, increasing their volume by 30%. Finally, microspheres loaded with methylene blue were able to release the dye gradually, obeying second-order kinetics for times less than 600min. This behavior suggests that diffusion is governed by the relaxation of polymer chains in the swelled state, thus facilitating drug release outside the microspheres.