Fabrication of a curcumin encapsulated bioengineered nano-cocktail formulation for stimuli-responsive targeted therapeutic delivery to enhance anti-inflammatory, anti-oxidant, and anti-bacterial properties in sepsis management

This study aimed to fabricate an eco-friendly functionalized chitosan (CS) nanocarrier to establish a pH-responsive drug delivery system for the treatment of sepsis. Curcumin (Cur) and cerium oxide (CeO2) were loaded onto an octenylsuccinic anhydride (OSA)-functionalized CS nanoformulation (Cur@Ce/OCS) to achieve an effective nanocarrier (NC) for sepsis treatment. The physicochemical characteristics of the developed nanocarriers were determined using various characterization techniques. The developed CeO2-OCS nanoformulation has been showed effective anti-bacterial activity (similar to 97%) against G(+) and G(-) bacterial pathogens, and also have improved drug loading (94% +/- 2), and encapsulation efficiency (89.8% +/- 1.5), with uniform spherical particles having an average diameter of between 100 and 150 nm. The in vivo experimental results establish that Cur-loaded Ce/OCS NPs could have enhanced therapeutic potential against lung infection model by reducing bacterial burden and extensively decreasing inflammatory responses in sepsis model. Additionally, we determined the in vivo biosafety of the nanoformulations by histological observation of different mouse organs (heart, liver, spleen, and kidney), and observed no signs of toxicity in the treatment groups. The findings of this study clearly demonstrate the therapeutic potential of pH-sensitive nanoplatforms in the management of infectious sepsis.