Assessment of antimicrobial activity of melittin encapsulated in bicontinuous microemulsions prepared using renewable oils

The objective of this study is to demonstrate that melittin, a
well-studied antimicrobial peptide (AMP), can be solubilized in an active
form in bicontinuous microemulsions (BMEs) that employ biocompatible oils.
The systems investigated consisted of Winsor-III and -IV BME phases
composed of Water/Aerosol-OT (AOT)/Polysorbate 85/isopropyl myristate and
a Winsor-IV BME employing Polysorbate 80 and limonene. We found that
melittin resided in an a-helix-rich configuration and was in an apolar
environment for the AOT/Polysorbate 85 Winsor-III system, suggesting that
melittin interacted with the surfactant monolayer and was in an active
conformation. An apolar environment was also detected for melittin in the
two Winsor-IV systems, but to a lesser extent than the Winsor-III system.
Small-angle X-ray scattering analysis indicated that melittin at a
concentration of 1.0 g/Laq in the aqueous subphase of the Winsor-IV
systems led to the greatest impact on the BME structure (e.g., decrease of
quasi-periodic repeat distance and correlation length and induction of
interfacial fluidity). The antimicrobial activity of the Polysorbate 80
Winsor-IV system was evaluated against several bacteria prominent in
chronic wounds and surgical site infections (SSIs). Melittin-free BMEs
inhibited the growth of all tested bacteria due to its oil, limonene,
while the inclusion of 1.0 g/Laq of melittin in the BMEs enhanced the
activity against several bacteria. A further increase of melittin
concentration in the BMEs had no effect. These results demonstrate the
potential utility of BMEs as a delivery platform for AMPs and other
hydrophilic and lipophilic drugs to inhibit antibiotic-resistant
microorganisms in chronic wounds and SSIs.