Colloidal Structure Dictates Antimicrobial Efficacy in LL-37 Self-Assemblies With Glycerol Monooleate

Area of Science:

• Biomaterials Science
• Antimicrobial Peptides
• Nanotechnology

Background:

• The antimicrobial peptide LL-37 is a potential antibiotic alternative, with its therapeutic efficacy potentially enhanced by self-assembly with lipids.
• Glyceryl monooleate (GMO) can form various colloidal structures like cubosomes and vesicles, influencing the properties of co-assembled molecules.

Purpose of the Study:

• To investigate the self-assembly of LL-37 with GMO and correlate the resulting colloidal structures with antimicrobial activity.
• To determine the impact of different LL-37/GMO structures on planktonic and biofilm bacterial growth.

Main Methods:

• Small-angle X-ray scattering (SAXS), dynamic light scattering (DLS), and cryogenic transmission electron microscopy (cryo-TEM) were used to characterize LL-37/GMO structures.
• In vitro antimicrobial assays were performed against *Pseudomonas aeruginosa* and *Staphylococcus aureus* planktonic and biofilm cells.

Main Results:

• Increasing LL-37 content in GMO induced structural transitions from inverse bicontinuous cubosomes to multilamellar vesicles and then to direct rod-like mixed-micelles.
• LL-37/GMO cylindrical micelles (9/1 and 8/2 ratios) demonstrated significant reduction (6-log) of *P. aeruginosa* planktonic cells.
• Cubosomes and vesicles showed limited activity against *P. aeruginosa* and *S. aureus*, with vesicles even promoting *S. aureus* biofilm biomass.

Conclusions:

• The colloidal structure formed by LL-37 and GMO is critical for determining antimicrobial efficacy.
• Rod-like mixed-micelles represent a promising nanocarrier structure for LL-37's antibacterial activity, whereas cubosomes and vesicles are less effective.
• These findings provide insights for designing advanced lipid nanocarriers for enhanced antimicrobial therapies.