The chitosan/cellulose nanocrystal cross-linked carriers effectively encapsulate ursolic acid to enhance the delivery of bioactive natural products

The druggability of bioactive natural products (BNPs) is limited and their potential as medicines faces significant challenges. In this study, we developed a high adhesion, dual-stimulation-responsive drug release system (UA@CS/CNCs), using chitosan (CS) and cellulose nanocrystal (CNC) as the raw material and sodium alginate (SA) as the capping agent for the regulated release of ursolic acid (UA). The results demonstrated that the optimal encapsulation efficiency of UA was achieved at a mass ratio of 1:2 between CS and CNC. The UA@CS/CNCs developed in this study exhibited rapid drug release in alkaline and high temperature settings, demonstrating excellent pH-temperature responsive performance. The results of bacterial inhibition experiments demonstrate that the UA@CS/CNCs nanodrugs exhibit significant antibacterial activity against P. infestans, with a bacterial inhibition rate of 60.4%. Additionally, the abundant hydroxyl groups in CNCs enhance hydrogen bonding and electrostatic interactions, improving adhesion to crop leaves and enhancing carrier wettability. Drug release into non-target environments was effectively prevented by encapsulating UA in nanocarriers, which significantly reduces toxicity to zebrafish. Consequently, the nanodrugs of UA@CS/CNCs exhibited enhanced potential for targeted efficacy and environmental safety.