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

• Published in: Advanced functional materials 2019-08, Vol.29 (35), p.n/a
• Main Authors: Zabara, Mahsa, Senturk, Berna, Gontsarik, Mark, Ren, Qun, Rottmar, Markus, Maniura‐Weber, Katharina, Mezzenga, Raffaele, Bolisetty, Sreenath, Salentinig, Stefan
• Format: Article
• Language: English
• Subjects: antibacterial nanocarriers; Antibiotics; Antiinfectives and antibacterials; Antimicrobial agents; antimicrobial peptides; Bacteria; Biocompatibility; cell proliferation; Light scattering; Lipids; Materials science; Micelles; SAXS; stabilizer‐free cubosomes; Toxicity; Wound healing
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.201904007

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. The study demonstrates cytocompatible, antimicrobial nano‐biointerfaces that promote cell proliferation with the potential for applications in wound healing. This is achieved by assembling stabilizer‐free lipid cubosomes and functionalising them with the antimicrobial peptide LL‐37. The peptide spontaneously integrates into the cubosomes forming the multifunctional nanomaterials. The stabilizer‐free design of lipid nanocarriers holds great promise for advanced drug delivery materials.