Dual-tuned drug release by nanofibrous scaffolds of chitosan and mesoporous silica microspheres

Abstract
A sustained drug release with an initial burst release followed by a linear release to optimally maintain the drug concentration in the therapeutic region is highly desirable for medicine administration. This study describes a method for the preparation of chitosan and chitosan–silica scaffolds and assesses their use for sustained release of curcumin. Porous chitosans with nanofibrous or sheet-like morphologies are fabricated from aqueous curcumin–chitosan solutions by a freeze-drying approach. The pore morphology can influence the release rate; curcumin was released much faster from the nanofibers than from the macroporous scaffolds. Amine-modified mesoporous silica microspheres are added into chitosan as another control; the release rate decreases due to the interaction of amine groups on silica and curcumin with chitosan. The silica microspheres with tuneable loading of curcumin are further incorporated into the curcumin–chitosan scaffold. The curcumin release into phosphate buffer solutions at 37 °C shows a two-stage release profile with distinctly different release rates. The high permeability and hydrophilic property of chitosan result in the initial burst release. The slow near-linear release at the 2nd stage results from the loaded silica microspheres. Loading of curcumin, concentration of chitosan, and content of silica microspheres in the composites are investigated and the effects on the release profiles are demonstrated. The present method is further adapted to prepare thin films with reasonable strength and flexibility by air drying and freeze drying. The tuneable sustained release of curcumin is also shown for the films.