Bioinspired mycobacterial lipid coating of porous particles for enhanced antimicrobial efficacy

The study aimed to investigate the unique lipid composition of Mycobacterium bovis BCG and its potential to enhance antimicrobial efficacy of lipid-coated mesoporous silica particles (MSPs). The bacterial lipids (BL) were extracted with petroleum ether and analyzed via LC-MS, revealing a complex mixture of phospholipids, including cardiolipin, phosphatidylcholine, phosphatidylethanolamine, and triacylglycerols. Lipid coating (using bacterial lipids and lung surfactant DPPC as the main component) was performed on MSPs via vesicle fusion approach and confirmed with ATR-FTIR spectroscopy. MSPs were loaded with clofazimine (CLZ), as a drug model for tuberculosis. The obtained BL-DPPC-coated CLZ-MSPs were more effective in inhibiting mycobacterial growth and killing intracellular mycobacteria compared to uncoated and DPPC-coated CLZ-MSPs. The bacterial lipids showed a good safety profile on M1-like and M2-like human primary macrophages without inducing a strong immune response or formation of foam cells. These findings suggest that the obtained bacterial lipid coatings can improve antimicrobial efficacy in treating both extracellular and intracellular mycobacteria infections directly in the lungs.