The preparation of casein-chitosan based naringin nanoparticles and their therapeutic application against Pseudomonas aeruginosa-induced pneumonia.

Naringenin is a natural dihydro-flavonoid compound with various beneficial pharmacological activities. However, the extremely poor water solubility and bioavailability pose significant challenges for its application. In this study, chitosan-casein-naringenin nanoparticles (Cs-cas-Nar) were prepared to enhance naringenin's water solubility and bioavailability. Cs-cas-Nar had a particle size of 225.8 nm, a PDI of 0.155, a zeta potential of 27.2 mV, and an encapsulation efficiency of 87.02 %. FT-IR analysis indicated that casein encapsulated naringenin through hydrogen bonds and non-covalent interactions. Simulated gastrointestinal digestion and in vivo release results demonstrated that Cs-cas-Nar significantly improved naringenin's water solubility and bioavailability. The site-controlled and rapid release of Cs-cas-Nar provided higher drug concentration in the intestine and lung tissue. In in vivo experiments, Cs-cas-Nar provided a protective effect against Pseudomonas aeruginosa-induced pneumonia in mice. Cs-cas-Nar not only reduced weight loss and lung bacterial load of pneumonia mice, but also reduced the production of pro-inflammatory factors IL-1β and IL-6 by >50 % and restored the antioxidant capacity of the lungs. Through computer simulation technology and qPCR detection, we confirmed that Cs-cas-Nar can inhibit the assembly of P. aeruginosa flagella. These findings suggest that Cs-cas-Nar is a simple and easily manufactured formulation with potential application value in treating P. aeruginosa infection.