Intragastric amorphous calcium carbonate consumption triggered generation of in situ hydrogel piece for sustained drug release

Sustained-release systems in solid forms are widely accepted except for those patients with dysphagia such as the elderly and infants. Herein, we have developed a sustained-release oral drug solution by dispersing polyaspartic acid stabilized amorphous calcium carbonate (ACC) nanoparticles (NPs) (<100 nm) in drug-containing sodium alginate (SA) solution (2%). It can be supposed that ACC NPs would consume in the gastrointestinal tract acid environment and provide calcium ions as the crosslinker for SA polymer solution to gain in situ hydrogels. The pre-gel solution system appeared a distinct reversible shear-thin characteristic with high viscosity and stability during storage. Whereas, it can regain fine flowability for convenient oral administration after slightly shaking. In this study, ACC NPs consumption triggered solution-gel transition of this drug-containing pre-gel solution system was demonstrated in simulated gastric solution and in vivo, with the distinct sustained drug release profiles lasting for 10 h. In addition, pharmacokinetics studies in SD rats showed that the Tmax (up to 1.79 ± 0.24 h) and AUC0-12 (46.37 ± 2.71 μg/mL·h) of ACC/SA in situ hydrogels treated group were significantly higher (p < 0.05) than that of free drug solution. Overall, these results highlighted a novel promising platform for oral administration of drugs, reduced dosing frequency, and high potential compliance for patients with dysphagia.