Bovine serum albumin nanoparticles improve bacteriophage stability and antimicrobial activity against Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic pathogen characterized by high antimicrobial resistance, which poses significant challenges for treatment. Phage therapy offers a targeted alternative but is limited by the poor stability of phage and phage cocktails under physiological conditions. Here, we report the encapsulation of the anti-P. aeruginosa phage VAC1 in bovine serum albumin (BSA) nanoparticles (NPPha) to increase their stability and antimicrobial performance. NPPha displayed high encapsulation efficiency (> 95%), sustained phage release, and preserved infectivity for up to five days at 37 °C, while showing no cytotoxicity in HepG2 cells. In vitro, compared with free VAC1, NPPha significantly reduced bacterial growth and promoted a > 10⁵-fold increase in phage replication. In a murine model of acute lung infection, NPPha reduced the bacterial burden, increased phage recovery in the lungs, and lowered tissue injury, although survival rates did not improve. These findings highlight the use of albumin-based nanoparticles as a simple, low-cost strategy to stabilize bacteriophages and potentiate their antibacterial activity, with potential applications in phage therapy against multidrug-resistant P. aeruginosa.