Development of plantaricin RX-8 loaded pectin/4-carboxyphenylboric acid/carboxymethyl chitosan hydrogel microbead: A potential targeted oral delivery system

Bacteriocin can effectively improve the gut inflammation for their superior antibacterial activity. However, its inherent attributes, such as easily degraded and off-target effect in the gastrointestinal environment, make bacteriocins' efficient oral delivery a great challenge. Herein, a pectin/4-carboxyphenylboric acid/carboxymethyl chitosan (PEC/CPBA/CMCS) hydrogel microbead targeted oral delivery system was innovatively developed for the plantaricin RX-8 protective delivery, precisely targeted inflammatory microenvironment (IME) and sustained released plantaricin RX-8 by pH/ROS dual stimulation response. The hydrogel microbeads showed regular in shape and size, and exhibited high affinity for sialic acid of tumor cells. Subsequently, hydrogel microbeads exhibited the protective effect in gastrointestinal tract to avoid plantaricin RX-8 leakage, whereas in simulated normal environment and simulated IME showed better swelling and sustain release behaviors. Notably, the plantaricin RX-8 retains antibacterial activity in the simulated environments. Importantly, hydrogel microbeads showed no toxicity and inhibited tumor cell proliferation, which was ascribed to the sustained release of plantaricin RX-8 under ROS-sensitive IME, as validated by in vivo fluorescence imaging. Microbead not only demonstrated biodistribution in high potency, but also exhibited remarkable anti-inflammatory properties in alleviating colitis in vivo. The present study highlights the promising application of hydrogel carriers for improved oral delivery approach of bacteriocin bioavailability.