Multifunctional Nano-Biointerfaces: Cytocompatible Antimicrobial Nanocarriers from Stabilizer-Free Cubosomes

The rational design of alternative antimicrobial materials with reduced toxicity toward mammalian cells is highly desired due to the growing occurrence of bacteria resistant to conventional antibiotics. A promising approach is the design of lipid-based antimicrobial nanocarriers. However, most of the commonly used polymer-stabilized nanocarriers are cytotoxic. Herein, the design of a novel, stabilizer-free nanocarrier for the human cathelicidin derived antimicrobial peptide LL-37 that is cytocompatible and promotes cell proliferation for improved wound healing is reported. The nanocarrier is formed through the spontaneous integration of LL-37 into novel, stabilizer-free glycerol mono-oleate (GMO)-based cubosomes. Transformations in the internal structure of the cubosomes from Pn3m to Im3m-type and eventually their transition into small vesicles and spherical micelles are demonstrated upon the encapsulation of LL-37 into their internal bicontinuous cubic structure using small angle X-ray scattering, cryogenic transmission electron microscopy, and light scattering techniques. Additional in vitro biological assays show the antimicrobial activity of the stabilizer-free nano-objects on a variety of bacteria strains, their cytocompatibility, and cell-proliferation enhancing effect. The results outline a promising strategy for the comprehensive design of antimicrobial, cytocompatible lipid nanocarriers for the protection and delivery of bioactive molecules with potential for application as advanced wound healing materials.