Size-tailored and acid-degradable polyvinyl alcohol microgels for inhalation therapy of bacterial pneumonia.

Administration of antibiotics via inhalation is considered an effective strategy for pneumonia treatment; however, it encounters challenges related to the development of drug formulations with precise particle sizes and controlled release profiles. Herein, size-tailored and acid-degradable polyvinyl alcohol (PVA) microgels are utilized for nebulized inhalation delivery of piperacillin (PIP) antibiotics to effectively treat pneumonia. These microgels loaded with PIP (G@PIP) were prepared through the UV-crosslinking of thermo-triggered vinyl ether methacrylate-functionalized PVA (PVAVEMA) micro-aggregates in aqueous solution. The size of G@PIP microgels could be tailored by adjusting concentrations during the crosslinking process above phase-transition temperature at 15 °C. Additionally, under simulated inflammatory acidic conditions, the G@PIP microgels degraded and released PIP with relatively high inhibition efficiency against E. coli. Furthermore, in vivo therapeutic outcomes revealed that inhalational delivery of G@PIP microgel with a medium-size of 3.5 μm (G-3.5@PIP) exhibited superior lung deposition compared to other microgel sizes owing to its reduced exhalation and enhanced diffusion capacity within the pulmonary system. The high accumulation of G-3.5@PIP significantly reduced E. coli infection and associated inflammation while maintaining the biocompatibility of the microgels. Overall, these acid-degradable PVA microgels offer a versatile and efficacious inhalation therapy for pneumonia-associated infections.