Donepezil hydrochloride-reinforced cellulose nanocrystal-aggregated gel structure for long-acting drug delivery.

A donepezil hydrochloride (DPZ)-reinforced cellulose nanocrystal (CNC) hydrogel structure with pH control was developed for sustained drug delivery through subcutaneous injection. In the present study, an aggregated CNC gel was fabricated by reducing the electrostatic repulsion between CNC particles by incorporating DPZ and adjusting the pH value to 7.7. The crosslinked CNC/DPZ (cCNC/DPZ) gel exhibited immediate gelation, injection capability through a single syringe, improved viscoelasticity, and shear-thinning properties. Interactions between the CNCs and DPZ and pH regulation were assessed using several solid-state studies, and a sustained release profile of the DPZ from the cCNC/DPZ gel was also observed. In the pharmacokinetic study, a higher half-life and mean residence time and lower maximum drug concentration values were obtained in the cCNC/DPZ group than in the DPZ solution and CNC/DPZ groups after subcutaneous injection. Drug salt form-incorporated and pH-controlled CNC hydrogel systems can be safely applied to the subcutaneous delivery of DPZ.