Preparation of water-soluble nanoconjugates of antimicrobial peptide HF-18 with polyacrylic acid: implications for environmental stress resistance

Abstract The low stability of antimicrobial peptides (AMPs) represents a major barrier to their clinical application despite their promise as therapeutic agents. This study aims to enhance the stability of the HF-18 peptide by conjugating it with polyacrylic acid (PAA), focusing on improving resistance to environmental stress conditions such as varying pH and high temperatures. In this conjugation process, different peptide-polymer ratios were explored using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) as a cross-linker. Comprehensive characterization of the resulting nanoconjugates was carried out using size exclusion chromatography, UV–vis spectroscopy, fluorescence spectroscopy, size and zeta potential analyses. Stability assessments indicated that the HF-18/PAA nanoconjugates exhibited significantly enhanced resilience compared to the free HF-18, particularly under acidic and high-temperature conditions. These findings suggest that conjugation with PAA effectively improves the stability of HF-18, making it more suitable for potential applications that require robustness against harsh environmental factors. This approach presents a promising strategy to overcome the limitations of AMP stability and broaden the scope of peptide-based therapeutics. The findings from the research conducted on the model antimicrobial peptide-polymer conjugate system, whose physicochemical properties and stability have been demonstrated, suggest a promising basis for future treatments of bacterial infections.