Construction of an environmentally friendly octenylsuccinic anhydride modified pH-sensitive chitosan nanoparticle drug delivery system to alleviate inflammation and oxidative stress

An environmentally friendly octenylsuccinic anhydride modified pH-sensitive chitosan-octenylsuccinic anhydride (OSA-CS) was synthesized. The critical micelle concentration (CMC) of the modified chitosan was 27 μg/mL, the graft polymers can form solubilized curcumin (CUR) and quercetin (QUE) nanoparticles. The drug-loaded nanoparticles had high encapsulation efficiency and drug loading content, the self-assembly of graft polymers formed spherical uniform nanoparticles with an approximate diameter of 150-180 nm. The nanoparticles were stable under storage conditions and in serum. The results revealed that OSA-CS exhibited excellent biocompatibility, no cytotoxicity. Additionally, the results of pH sensitivity and drug release experiments showed that the nanoparticles were highly sensitive to weakly acidic conditions (pH 6.0) and showed a faster release rate, while they were reasonably stable at physiological conditions (pH 7.4). The drug-loaded nanoparticles exhibited higher cellular uptake in vitro, and exhibited stronger anti-inflammatory and antioxidant efficacy. Therefore, OSA-CS-based nanoparticles are a promising hydrophobic drug delivery system for pH-response targeting therapy.