Antimicrobial Peptides Expressed by the Polyaminoglycoside Nanosystem for Bacterial Peritonitis Management via Inflammation Modulation

Peritonitis, a prevalent and dangerous condition, can result from trauma, surgery, liver cirrhosis, peritoneal dialysis, and gastrointestinal issues. If not effectively managed, it can cause systemic infection, leading to complications, such as sepsis and bacteremia. LL37, an antimicrobial peptide of the innate immune system, exhibits broad-spectrum antibacterial activity and potent immune-modulating functions, serving as a critical defense against infections. In this study, we developed a combined system delivering a therapeutic plasmid (pLL37) via cationic poly(aminoglycoside) (SS-HPT) to treat bacterial peritonitis in immunocompromised populations. This system combines direct antimicrobial action and inflammation modulation. The SS-HPT carrier, containing tobramycin, provides immediate antibacterial effects by inhibiting the bacterial protein synthesis. Simultaneously, the expressed LL37 peptide enhances bacterial membrane disruption and modulates the inflammatory response by regulating cytokine release and immune cell differentiation. Treatment efficacy was comprehensively evaluated using survival rate assessments, clinical symptom analysis, inflammatory marker detection, histopathological observation, and molecular biological methods. Results indicated that the system significantly improved survival rates, reduced inflammatory responses, and ameliorated histopathological damage, effectively preventing and treating bacterial peritonitis and its complications. In conclusion, the SS-HPT/pLL37 system offers a promising new strategy for the treatment of bacterial peritonitis.