Lipidic drug delivery systems: is the microbiome a cause for concern?

The formulation of ‘smart’ therapeutics has sparked an explosion of interest in lipidic nanomaterials. In vitro and in vivo tests for therapeutic agents have traditionally been run in sterile environments, but many target areas for drug delivery such as the gastrointestinal (GI) tract and skin are home to thousands of microbial species. Here, we examine the behaviour of lipidic nanomaterials after exposure to representative strains of four bacterial species found in several human microbiomes. Small angle x-ray scattering (SAXS) measurements show that the nanostructure of monoolein cubic and inverse hexagonal phases are transformed, respectively, into inverse hexagonal and inverse micellar cubic phase upon exposure to a strain of live Staphylococcus aureus often present on skin. Further investigations support that these transitions are due to enzymatic hydrolysis of constituent lipids. The structural transformations induced by S. aureus are shown to take place within a timeframe relevant to the therapeutic application of these materials, and significantly reduced the rate of drug release from monoolein-based nanomaterials. Interestingly, the representative strains of bacteria investigated from the GI tract (E. coli, L. rhamnosus) and in disease states (P. aeruginosa) had no effect on liquid crystal structure. These findings are the first to demonstrate how the live human microbiome can trigger changes in the structure and consequent drug release properties of lipidic nanomaterials. The effect appears to be strain specific, and varies from patient to patient, body region to body region, and is anticipated to affect the bioapplication of monoglyceride-based formulations.