Size-Tailored and Acid-Degradable Polyvinyl Alcohol Microgels for Inhalation Therapy of Bacterial Pneumonia

Inhalation administration of antibiotics 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 the 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 up on phase-transition temperature. 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 medium-size of 3.5 ?m (G-3.5@PIP) exhibited superior lung deposition compared to other microgels size 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 biocompatibility of the microgels. Overall, these acid-degradable PVA microgels offer a versatile and efficacious inhalation therapy for pneumonia-associated infections.

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