Formation of concentric multilayers in a chitosan hydrogel inspired by Liesegang ring phenomena

Liesegang rings, periodical bands or ring patterns formed by inorganic precipitation in polymer gel medium, have attracted lots of interest of researchers aiming to construct ordered structures. Inspired by the Liesegang ring phenomena, chitosan, instead of inorganic species, was used as building block to construct a chitosan hydrogel with concentric multilayers in a protonated chitosan/NaOH reaction system by alternate soaking in NaOH solution and water. The morphology of concentric multilayers structure was characterized by environmental scanning electron microscopy. The upload and release behavior of isoniazid was also investigated. The quantitive rules of the concentric layer position/the square root of reaction time and the position of the consecutive concentric layer coincide with the time law and space law of the classical Liesegang ring phenomena, respectively. The chitosan solution converts into a hydrogel accompanied by remarkable volume shrinkage due to hydrogen bonds reconstruction and electrostatic repulsion disappearance. The separated concentric multilayers can be formed due to the fluctuation of hydroxide ions concentration when the neutralization is interrupted by alternate soaking in NaOH solution and water. The major difference of the concentric multilayers in chitosan hydrogel from the classical Liesegang ring phenomena occurring in inorganic precipitation systems is that chitosan not only plays the role of reactant in chitosan hydrogel formation, but also acts as supporting reaction medium to control the diffusion behavior of hydroxide ions. The porosity and equilibrium swelling ratio of the chitosan xerogel are 63% and 1100%, respectively, which is feasible for drug uploading through diffusion or absorption. The isoniazid release kinetics are dominated by the diffusion-erosion model. The chitosan hydrogel with concentric multilayers structure loaded with isoniazid will have wide applications in treatment of bone tuberculosis.