Figure 4.

Schematic illustration of the targeted release of an antibiotic from pHresponsive nanocarriers into the interstices of a bacterium. The nanosystems were vancomycin-loaded micelles made of poly(lactic-co-glycolic acid)-b-polyhistidine-b- polyethylene glycol (PLGA-PLH-PEG) triblock copolymer. PLGA, PLH and PEG contributed to the core, interlayer and surface of the micelles, respectively. Vancomycin was loaded inside the hydrophobic core (PLGA block) of the micelles owing to its hydrophobicity. In the bloodstream, the pH was 7.4 and the micelles were stable at this physiological pH owing to the stealth property of hydrophilic PEG block on the micelle surface. The micelles would not be endocytosed by non-target cells owing to the slightly negative charge of PLH at physiological pH. At the site of infection, the pH was low and the high acidity ionized the polyhistidine component to render positive charges to the micelles. The positively charged micelles bound to the negatively charged bacterial cell wall, and subsequently released the loaded vancomycin antibiotic to kill bacteria. Adapted, with permission, from [43].