The lack of effective oral drug delivery systems to treat gastric ulcer is an urgent challenge in clinical practice. Herein, a gastric acid pH-responsive hydrogel of curcumin/sodium alginate/polyaspartic acid@CaCO3 (Cur/SA/PC) was developed for sustained release of Cur, exerting effective protection and treatment of gastric ulcers. The in vitro gelatinization properties and the corresponding gel characteristics of the SA/PC delivery system demonstrated the successful construction of the in situ hydrogel with uniform strength. The cellular uptake illustrated the successful uptake and sustained release of Cur. Besides, Cur effectively inhibited NLRP3-mediated pyroptosis both in vitro and in vivo, exhibited an excellent pro-healing effect by regulating the PI3K/Akt signaling pathway, and alleviated acetic acid-induced chronic gastric injury in rats. Moreover, the relative bioavailability of Cur in the SA/PC hydrogel could effectively increase in the pharmacokinetic study. Importantly, the protective barrier formed by the SA/PC hydrogel could effectively protect against alcohol-induced acute gastric ulcers in rats. Overall, the designed SA/PC oral delivery system is a promising strategy to overcome gastric barriers for oral drug delivery.
Keywords: NLRP3 inflammatory signaling pathway; SA/PC in situ hydrogels; gastric acid response; gastric ulcers.