pH ‐sensitive polyion nanocomplexes for antimicrobial peptide delivery

As an alternative to antibiotics, antimicrobial peptides (AMPs) are attracting more and more attention for non-antibiotic antibacterial therapy. However, there are still many issues of AMPs for clinical applications. For example, AMPs are generally positively charged and can be easily cleared during blood circulation. In addition, the cationic AMPs show strong cytotoxicity, which brings potential biosafety risks. In order to address these issues, pH-sensitive polyion nanocomplex is designed for the delivery of AMPs by electrostatic self-assembly of positively charged AMPs Magainin-I and negatively charged 2,3-dimethyl maleic anhydride (DA) modified epsilon-polylysine (EPL) (EPL-DA). The size and surface charge of the polyion nanocomplex is fully investigated by dynamic laser scattering (DLS) and transmission electron microscope (TEM). Magainin-I loaded polyion nanocomplex is stable in physiological environment (pH 7.4), which can effectively reduce the cytotoxicity of AMPs. In the slightly acidic environment (pH 5.0-6.0) in bacteria infected tissue, the nanocomplex would be disintegrated to positively charged EPL and Magainin-I, thereby restoring antibacterial properties. The excellent antibacterial activity of Magainin-I loaded polyion nanocomplexes is confirmed by a series of in vitro antibacterial experiments. The fabrication of polyion nanocomplex provides an innovative way for the delivery of AMPs.