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Fucose-tobramycin sponge-like microparticles to treat pulmonary Pseudomonas aeruginosa infections in a lectin-competitive approach.

Yuzhen Jin,Jun Chen,Cenfeng Liu,Wenhao Wang,Yue Zhou,Kaiqing Zhang,Xiaolu Xiao,Guixiang Chen,Xuejuan Zhang,Zhengwei Huang,Chuanbin Wu,Ying Huang

Published 2025 in Journal of Advanced Research

ABSTRACT

INTRODUCTION The high incidence of pulmonary infections caused by multidrug-resistant bacteria such as Pseudomonas aeruginosa (PA) poses significant treatment challenges. Dry powder inhaler (DPIs) are an effective treatment method, delivering antibiotics directly to lung lesions. However, DPIs face two main issues: abnormal respiratory variability causes inadequate pulmonary deposition and PA's biofilms hinder antibiotic access. OBJECTIVES A sponge-like dry powder based on the lectin-competitive strategy was developed with tobramycin (TOB) to solve the crucial issue. METHODS Lectin-affinity sugars were screened using isothermal titration calorimetry. Sponge-like TOB-Formulation were then developed with the selected sugar as a carrier via spray freeze-drying. The formulation with the highest lung delivery efficiency was identified with a next-generation impactor and validated in a rat model of chronic pulmonary infection. RESULTS Fucose was used as a carrier to develop sponge-like TOB- Formulation by spray freeze-drying technology with spherical low-density and nanoporous particles, making them suitable for patient's inspiratory mode and improving lung deposition. Among them, the F2 (3% solid content) exhibited the highest fine particle fraction value of 60.01%, which can against the abnormal respiratory variability in dyspnea patients under diverse airflow rates and inhalation modalities. In the in vivo model of chronic pulmonary infections in rats, F2 demonstrated a significantly superior anti-bacterial, anti-inflammatory and improved lung function compared to the tobramycin inhalation solution. CONCLUSION This tobramycin spongy-like dry powder, identified as high lectin affinity and excellent respiratory variability tolerance, holds significant promise for the treatment of pulmonary infections.

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