Biocompatible Double-Membrane Hydrogels from Cationic Cellulose Nanocrystals and Anionic Alginate as Complexing Drugs Codelivery.

A biocompatible hydrogel with a double-membrane structure is developed from cationic cellulose nanocrystals (CNC) and anionic alginate. The architecture of the double-membrane hydrogel involves an external membrane composed of neat alginate, and an internal composite hydrogel consolidates by electrostatic interactions between cationic CNC and anionic alginate. The thickness of the outer layer can be regulated by the adsorption duration of neat alginate, and the shape of the inner layer can directly determine the morphology and dimensions of the double-membrane hydrogel (microsphere, capsule, and filmlike shapes). Two drugs are introduced into the different membranes of the hydrogel, which will ensure the complexing drugs codelivery and the varied drugs release behaviors from two membranes (rapid drug release of the outer hydrogel, and prolonged drug release of the inner hydrogel). The double-membrane hydrogel containing the chemically modified cellulose nanocrystals (CCNC) in the inner membrane hydrogel can provide the sustained drug release ascribed to the "nano-obstruction effect" and "nanolocking effect" induced by the presence of CCNC components in the hydrogels. Derived from natural polysaccharides (cellulose and alginate), the novel double-membrane structure hydrogel material developed in this study is biocompatible and can realize the complexing drugs release with the first quick release of one drug and the successively slow release of another drug, which is expected to achieve the synergistic release effects or potentially provide the solution to drug resistance in biomedical application.