Liposome of a synergistic combination of HDP-mimicking polymer and rifampicin for treating bacterial infections in aquaculture via oral administration

The extensive use of antibiotics in high-density aquaculture has accelerated the emergence of antibiotic-resistant bacteria. The presence of antibiotics in water and soil, and their transmission through the food chain exacerbate the pressures associated with antibiotic resistance, posing a significant threat to human health. Despite this challenge and serious issue, effective alternatives to antibiotics remain lacking. In this study, we report a potent synergistic effect between an HDP-mimicking polymer, ^DLLys₉₀-BLG₁₀, and rifampicin against Vibrio species. This synergistic combination substantially reduces the required dosage of rifampicin, thereby mitigating the risk of antibiotic resistance development and the release of rifampicin into water and soil. Furthermore, we developed a cell-penetrating peptide-modified liposome system that can co-encapsulate ^DLLys₉₀-BLG₁₀ and rifampicin, which exerts potent antibacterial activity against Vibrio both in vitro and in vivo, while maintaining bio-compatibility. Additionally, oral administration of CPP-Lip@Syn showed effective control of Vibrio infections. This strategy opens new avenues in exploring antibiotic alternatives in aquaculture and implies potential applications in aquaculture.