Chemical modification of alginate via the oxidation-reductive amination reaction for the development of alginate derivative electrospun composite nanofibers

Abstract

To examine if the improvement of the molecular flexibility for the reductive-amination of oxidized alginate derivative (RAOA) through chemical modification could be conducive to the enhancement of alginate electrospinnability, we attempted to use the electrospinning technology to develop the alginate derivative electrospun composite nanofibers that can load the hydrophobic anti-inflammatory drug, ibuprofen, with the aid of polyvinyl alcohol (PVA). The synthesized RAOA was examined by FT-IR spectrometer, 1H NMR spectrometer and fluorescence spectrophotometer. Furthermore, the effects of surface tension, electrical conductivity and rheological properties of the RAOA/PVA blend solution on the electrospinning property and fiber morphology of the resultant RAOA/PVA electrospun composite nanofibers were explored by surface tension meter, conductivity meter, rheometer and SEM. Subsequently, the drug loading and release mechanism of ibuprofen from the RAOA/PVA electrospun composite nanofibers were analyzed through the simulated drug release test. In addition, the cytotoxicity of the RAOA/PVA electrospun composite nanofibers was also evaluated with L929 cells by Cell Counting Kit-8 (CCK-8) assay. Experimental results showed that the hydrophobic side groups were successfully grafted onto the alginate backbone by the oxidation-reductive amination reaction, which destroyed the intramolecular hydrogen bond of the raw sodium alginate (SA), thus enhancing the molecular flexibility and colloidal interface activity of RAOA. So the RAOA could exhibit good amphiphilic property with the critical aggregation concentration (CAC) of 0.42 g/L in NaCl solution, and form the self-assembled micelle with the average hydrodynamic diameter of 615 nm (PDI = 0.24) and zeta potential at about −66.5 mV. Although the oxidation-reductive amination reaction for the modification of RAOA could not fundamentally achieve the generation of bead-free nanofibers by electrospinning of single RAOA aqueous solution, it could improve the electrospinning performance of RAOA/PVA blend solution and increase its content in the RAOA/PVA electrospun composite nanofibers. Furthermore, the fabricated RAOA/PVA electrospun composite nanofibers exhibited the high encapsulation efficiency (EE) and sustained-release property in comparison with the 50/50 SA/PVA electrospun composite nanofibers, due to the good affinity of RAOA to hydrophobic ibuprofen that achieve the loading and controlled release of the hydrophobic drug. Besides, the RAOA/PVA electrospun composite nanofibers exhibited low cytotoxicity to L929 cells. Therefore, the resultant RAOA/PVA electrospun composite nanofibers, combining the structural characteristics of the electrospun nanofibers and the properties of RAOA including the good self-assembly performance, colloidal interface activity, sustained release performance and good cytocompatibility, may possess great potentials as the functional wound dressings for biomedical applications.