Enhancement of Fowlicidin-1's Therapeutic Efficacy: Mitigation of Toxicity via a Chitosan Cross-Linked Nanocarrier System

Method: In this study, Fowlicidin-1 was encapsulated into chitosan nanoparticles formed via ionic gelation. The formulation was optimized for encapsulation efficiency, particle size, and surface charge. Antimicrobial activity was evaluated against resistant bacterial strains, while cytotoxicity was assessed using hemolysis and cell viability assays. Results: The chitosan nano-carrier system effectively preserved the antimicrobial potency of Fowlicidin-1 and significantly reduced its cytotoxicity. Encapsulated Fowlicidin-1 demonstrated reduced hemolytic activity and improved safety compared to the free peptide. method: A chitosan cross-linked nano-carrier system was engineered to encapsulate Fowlicidin-1. Chitosan was chosen due to its biocompatibility, biodegradability, and ability to form stable cross-linked networks that can modulate the release of encapsulated agents. The formulation process was optimized to ensure effective encapsulation of Fowlicidin-1 while maintaining its structural integrity and antimicrobial properties. The nano-carrier system was then rigorously tested to assess its performance in preserving the peptide’s antimicrobial activity and reducing its cytotoxicity. Key evaluations included antimicrobial assays against resistant bacterial strains and cytotoxicity assessments on mammalian cell lines, with particular attention given to the degree of hemolysis in human erythrocytes. Discussion: Nano-encapsulation using a chitosan-based delivery system successfully mitigates the cytotoxic limitations of AMPs without compromising antimicrobial efficacy. This approach may enhance the clinical applicability of AMPs as alternatives to traditional antibiotics. Conclusion: The developed chitosan-based cross-linked nanocarrier system offers a promising strategy to reduce the cytotoxicity of AMPs, supporting their potential as safer and more effective antimicrobial therapeutics in the fight against antibiotic resistance.