Towards a drug delivery system based on branched fatty acids

Sammanfattning

The antibacterial properties of unbranched fatty acids have been reported in numerous studies. A particular molecule that has attracted some interest is 18-methyleicosanoic acid (18-MEA), a C20 fatty acid with a methyl branch on the 18th carbon. It has been shown to self-assemble into structures with inverse curvature at the water-air interface, where the tails are exposed on the outside of the curved surface. Furthermore, the curvature of these self-assembled structures can be tweaked by adding unbranched fatty acids. If this is reproducible in the bulk phase, it may be possible to tweak the curvature of aggregates in 18-MEA/water dispersions to create so-called cubosomes. These are discrete particles with an in-ternal inverse bicontinuous cubic (QII ) structure. Such particles have been shown to be intrinsically antibacterial, in addition to attracting attention as a possible drug delivery system. Cubosomes based on 18-MEA could thus constitute a novel antibacterial formulation with drug delivery capabilities. To investigate this hypothesis, water dispersions of 18-MEA with and without other lipids were prepared. Small angle x-ray scattering (SAXS) was then employed to determine the structure of the aggregates. The additional lipids were eicosanoic acid (EA), octadecanoic acid (OA), hexadecanoic acid (HA), and glyceryl monooleate (MO). Dispersions of 18-MEA alone formed a phase that could not be confidently determined, but is presumed to be micellar. Addition of EA, OA, and HA induced the formation of a lamellar phase. It was only upon addition of MO that QII phases could be observed. Both the primitive and diamond variants were observed for systems based on 18-MEA, 18-MEA:HA and 18-MEA:OA:HA with added MO. Notably, MO only needed to constitute 10% by weight of the lipid phase to form QII phases. Growth curves of the bacteria S. aureus in the presence of these dispersions were then measured, with conflicting results. Addition of dispersions increased the optical density of liquid bacteria cultures. Growth curves measured as fluorescence intensity mirrored this trend. However, the bacteria concentration as determined by a CFU experiment showed no significant effect of dispersion addition. The increase in optical density and fluorescence thus seem to be due to some confounding variable. There was evidence of clumping in the liquid cultures, which would explain especially the difference between the CFU and optical density measurements.