Lipidic drug delivery systems are responsive to the human microbiome

Area of Science:

• Biomaterials Science
• Microbiology
• Drug Delivery Systems

Background:

• Therapeutic agent testing often occurs in sterile conditions, disregarding the microbiome.
• Microbial communities inhabit many in vivo drug delivery sites, influencing therapeutic efficacy.
• Understanding microbial interactions with drug delivery systems is crucial for effective treatment.

Purpose of the Study:

• To investigate the impact of bacterial exposure on lipidic nanomaterials.
• To analyze structural and drug release changes in monoolein-based nanomaterials upon interaction with bacteria.
• To identify the mechanisms behind microbial-induced alterations in nanomaterial behavior.

Main Methods:

• Exposure of monoolein cubic and inverse hexagonal phases to bacterial strains.
• Small-angle X-ray scattering (SAXS) for nanostructure analysis.
• Assessment of drug release kinetics and investigation of hydrolysis and lipid transfer.

Main Results:

• Staphylococcus aureus exposure transformed monoolein nanostructures (e.g., cubic to inverse hexagonal).
• Bacterial enzymatic hydrolysis and lipid transfer were identified as key mechanisms.
• Structural changes led to a significant reduction in drug release rates.
• The observed effects were strain-specific and varied across individuals and body sites.

Conclusions:

• Live human microbiome species, like S. aureus, can alter lipidic nanomaterial structure and drug release.
• These microbial interactions pose challenges for monoglyceride-based drug delivery formulations.
• Findings highlight the need to consider the microbiome in nanomaterial design and application for in vivo use.