A targeted pH-responsive micelle based on poly (ethylene glycol) and polycaprolactone for Pseudomonas aeruginosa pneumonia treatment.

Bacterial pneumonia remains a critical global health challenge due to antibiotic resistance, biofilm-mediated drug tolerance, and unregulated inflammatory damage. Conventional therapies fail to address these interconnected issues, necessitating innovative delivery systems that combine antibacterial and anti-inflammatory actions. Given the microacidic environment of infected tissues, we developed an environmentally responsive micelle (FA-Cip/Ag-Ms) capable of targeting pseudomonas aeruginosa infected lungs, reducing bacterial load and suppressing inflammation. The micelle is self-assembled from the biblock copolymer PEG-Hyd-PCL, which was acid-sensitive due to the presence of hydrazone bond. The antibacterial agent ciprofloxacin (Cip) and the anti-inflammatory andrographolide(Ag) were encapsulated, while folate acid (FA) served as a targeting ligand on the surface. We characterized FA-Cip/Ag-Ms by (Alhajj et al., 2022 [1])HNM, FT-IR, and TEM, indicating that the micelle was successful preparation. The drug release of Cip was 50.6 % at pH 7.4, whereas 77.6 % accumulative release was achieved at pH 5.4. The targeting ability of FA was demonstrated by fluorescence microscopy detection of bacteria and cells and in vivo tissue imaging detection. The antibacterial and biofilm-clearing abilities of FA-Cip/Ag-Ms were confirmed by Live/Dead staining, and quantitative biofilm staining. Flow cytometry and cytokine analysis revealed reduced pro-inflammatory M1 macrophages and increased anti-inflammatory M2 polarization, accompanied by decreased IL-6 and elevated IL-10 levels. In a murine pneumonia model, FA-Cip/Ag-Ms significantly reduced lung tissue damage, inflammatory cell infiltration, and bacterial colony formation, while exhibiting good biocompatibility. This functional system integrates active targeting and microenvironment responsiveness, offering a promising strategy to improve therapeutic effect for bacterial pneumonia.